Search Results (484)

Background and Clinical Significance: Neurosarcoidosis (NS) is a rare manifestation of systemic sarcoidosis involving the central nervous system, with highly variable neurological and endocrine presentations. Among these, anterior pituitary dysfunction is particularly uncommon and diagnostically challenging. Case Presentation: We report the case of a 37-year-old woman with a 4-year history of secondary amenorrhoea and an initially suspected pituitary microadenoma, who was ultimately diagnosed with probable NS presenting with multiaxial anterior pituitary insufficiency. Early magnetic resonance imaging (MRI) revealed a small pituitary lesion and isolated pituitary stalk thickening, without other central nervous system abnormalities. Subsequent imaging demonstrated contrast-enhancing lesions involving the meninges and cranial nerves, along with progression of pituitary stalk involvement and loss of the posterior pituitary bright spot. Further evaluation confirmed systemic sarcoidosis. High-dose corticosteroid therapy led to partial clinical and radiological improvement; however, relapse necessitated methotrexate, and persistent pituitary hormone deficiencies required long-term hormonal replacement. Conclusions: This case highlights the diagnostic complexity of NS presenting with isolated endocrine dysfunction and subtle imaging findings. It underscores the need to consider systemic sarcoidosis in patients with unexplained hypopituitarism. Full article

Background/Objectives: Sarcoidosis is a granulomatous disease with no widely accepted circulating biomarkers for routine diagnostics. Soluble CD14 (sCD14) and lipopolysaccharide-binding protein (LBP), identified through extracellular vesicle proteomics, have been proposed as candidates. We aimed to compare the diagnostic accuracy of serum sCD14 and LBP with the established biomarker soluble interleukin-2 receptor alpha chain (sCD25). Methods: A matched case–control study included 46 newly diagnosed, untreated sarcoidosis patients and 46 age- and sex-matched healthy controls. Serum sCD14, sCD25, and LBP were quantified by ELISA. BMI was included as a covariate in multivariable logistic regression. Diagnostic performance was evaluated by ROC analysis and stepwise AIC model selection. Longitudinal biomarker dynamics were assessed in 32 patients under treatment. Results: sCD25 demonstrated superior diagnostic discrimination (AUC 0.92, 95% CI 0.87–0.98), compared with LBP (AUC 0.71, 95% CI 0.60–0.82) and sCD14 (AUC 0.61, 95% CI 0.49–0.73). In multivariate analysis, only sCD25 (OR per +100 pg/mL: 1.53; p < 0.001) remained an independent predictor of sarcoidosis. Neither LBP nor sCD14 improved model fit. All biomarkers significantly decreased following therapy. Conclusions: Among routinely measurable serum markers, sCD25 outperformed sCD14 and LBP in sarcoidosis diagnosis. Further studies should explore immunometabolic interactions to refine diagnostic algorithms. Full article

Cardiac sarcoidosis (CS) is a critical and frequently underdiagnosed phenotype of sarcoidosis, characterized by non-caseating granulomatous infiltration of the myocardium. This review synthesizes current knowledge regarding the pathogenesis, diagnosis, and management of CS. The disease manifests with a heterogeneous clinical spectrum ranging from asymptomatic conduction abnormalities to life-threatening ventricular arrhythmias and heart failure. Diagnosis remains challenging due to the patchy distribution of granulomas, which limits the sensitivity of endomyocardial biopsy. Consequently, a multimodal diagnostic approach is essential, integrating advanced imaging modalities such as cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) and ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET). These tools not only facilitate detection but also enable the differentiation of active inflammation from chronic fibrosis. Histopathological assessment, supported by specific immunophenotyping and electron microscopy, remains the gold standard for confirming diagnosis and excluding mimics like giant cell myocarditis or infectious granulomatous diseases. Management requires a multidisciplinary strategy combining immunosuppressive therapy, primarily corticosteroids and steroid-sparing agents, with guideline-directed cardiac care, including implantable cardioverter-defibrillators for arrhythmia risk stratification. Emerging biomarkers and artificial intelligence-driven imaging analysis promise to further refine risk stratification and therapeutic monitoring, advancing precision medicine in this complex disorder. Full article

Background: This study aims to characterize the clinical features and outcomes of tattoo-associated sarcoid-like uveitis using a multicenter uveitis registry given the limited existing data. Design: This is a retrospective study. Participants: Ten patients (20 eyes) diagnosed with tattoo-associated sarcoid-like uveitis took part in the study. Methods: The data of patients newly evaluated at participating registry centers from January 2000 to June 2025 were reviewed. Demographic data, treatments, visual acuity, recurrence, glaucoma/intraocular pressure (IOP)-lowering therapy, extraocular involvement, and histologic confirmation were extracted when available. Main Outcome Measures: Recurrence, glaucoma/IOP-lowering therapy, extraocular involvement, and change in logarithm of the minimum angle of resolution (logMAR) from presentation to final follow-up were measured. Results: Seven (70%) patients were male, and the patients’ mean age was 35.1 ± 7.8 years. All patients exhibited bilateral ocular involvement. Histologic confirmation at the tattoo site was documented in five (50%) patients. The mean logMAR visual acuity was 0.12 ± 0.31 at presentation and 0.16 ± 0.42 at the final follow-up (median follow-up: 20 months). All patients received topical corticosteroids; periocular steroids were administered in seven cases (70%), oral systemic steroids in four (40%), adalimumab in two (20%), and cyclosporin in one (10%). Seven cases (70%) developed uveitis recurrence, and eight received glaucoma/IOP-lowering therapy (80%). Extraocular inflammation affected the skin/tattoo in seven patients (70%) and the axillary lymph nodes in one (10%). This finding is definitive; however, this is also true even when the organ/body part is plural (e.g., lungs). Conclusions: Tattoo-associated sarcoid-like uveitis often follows a chronic course with frequent recurrence and uveitic glaucoma. Thus, close ophthalmic monitoring and coordinated systemic evaluation may be warranted. Full article

Myocarditis and inflammatory cardiomyopathy are inflammatory diseases of the heart muscle that can have both infectious and non-infectious causes. They can be caused by an unresolved viral infection or other infection, or they can be autoimmune, toxic, or allergic in nature. The specific identification of the pathogen and/or confirmation of inflammation can only be achieved through direct tissue analysis using endomyocardial biopsy (EMB), as neither detection of the virus nor assessment of the quality and intensity of the inflammation is possible using non-invasive methods. Accordingly, the removal and analysis of an EMB is considered the diagnostic gold standard in international guidelines and statements. The sudden onset of atypical angina pectoris and initially exertion-dependent dyspnea, as well as arrhythmias, pericardial effusion, and progressive symptoms of heart failure, indicate an acute inflammatory process of the myocardium. In addition, nonspecific symptoms such as fatigue and reduced physical performance may also occur. Diagnostic evaluation includes an electrocardiogram (ECG), cardiac imaging, and laboratory tests. The analysis of the EMB is crucial for a definitive diagnosis and thus for the initiation of an etiology-based, specific and personalized therapy. This includes histological and immunohistochemical inflammation diagnostics as well as molecular virological diagnostics. These enable both the detection of viruses and the assessment of transcriptional virus activity. New analyses using metagenomic next generation sequencing (NGS) techniques provide insights of enormous diagnostic and therapeutic relevance. This applies both to the spectrum of detectable pathogens and to the possibility of confirming transcriptional viral activity. In addition, gene expression profiling enables the differentiation of specific forms of myocardial inflammation (e.g., giant cell myocarditis, cardiac sarcoidosis, and eosinophilic myocarditis) and reduces the influence of “sampling errors” in focal inflammatory processes. The treatment of heart failure or ventricular arrhythmias is always symptomatic according to general evidence-based guidelines. In severe cases, mechanical circulatory support or even a heart transplant may be necessary. Patients with histologically confirmed myocardial inflammation or intramyocardial viral infection can be offered specific, causal, and personalized therapy. These patients can be successfully treated with immunosuppressive or antiviral therapy, which significantly improves the prognosis of the disease. Full article

Sarcoidosis is a multisystem granulomatous disease of unknown aetiology that frequently presents with mediastinal lymphadenopathy and often requires invasive diagnostic procedures. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is widely used in this setting; however, a definitive diagnosis cannot always be established at first attempt. This study aimed to identify clinical, laboratory, and radiological factors associated with a definitive diagnosis of sarcoidosis in patients referred for EBUS-TBNA. A retrospective analysis was performed including patients undergoing first-time ever EBUS-TBNA for mediastinal lymphadenopathy over a 12-month period. Demographic data, clinical features suggestive of sarcoidosis, chest computed tomography findings, and white blood cell count, were analysed, and definitive diagnoses were established based on cytological results and available follow-up data. Younger age (≤55 years), female sex, the absence of a pulmonary mass >10 mm on imaging, normal white blood cell count, and the presence of clinical features typical of sarcoidosis were significantly associated with a definitive diagnosis of sarcoidosis. Based on these variables, two point-based diagnostic scoring models were developed, demonstrating clinically relevant discriminatory performance. Readily available pre-procedural clinical and radiological factors may assist in estimating the probability of sarcoidosis in patients undergoing EBUS-TBNA for mediastinal lymphadenopathy and may support risk stratification and clinical decision-making. Full article

Background and Clinical Significance: Sarcoidosis is a systemic inflammatory disorder characterized by noncaseating granulomas. While pulmonary involvement is common, isolated renal involvement is rare and diagnostically challenging. We report a case emphasizing the utility of urinary tubular markers for early detection. Case Presentation: A 60-year-old woman with a history of suspected ocular sarcoidosis presented with progressive renal impairment and constitutional symptoms. Initial workup for systemic sarcoidosis was negative, leading to a misdiagnosis of chronic fatigue syndrome. Her rising serum creatinine was initially attributed to dehydration. However, a marked elevation in urinary β2-microglobulin (33,736 μg/L) prompted a renal biopsy, which revealed granulomatous tubulointerstitial nephritis. Following prednisolone therapy, her renal function improved, and her fatigue resolved completely. Conclusions: This case demonstrates that the kidney can be the primary site for histological diagnosis in the absence of pulmonary lesions. Incorporating urinary β2-microglobulin into routine monitoring may facilitate the early detection of renal sarcoidosis, preventing diagnostic delays. Full article

Cardiac magnetic resonance (CMR) has revolutionized the diagnosis and risk stratification of myocarditis. Beyond its capacity in detecting functional abnormalities, CMR is now capable of tissue characterization with high sensitivity and specificity, allowing for the identification of myocardial edema, hyperemia, and necrosis/fibrosis. The introduction of the Lake Louise Criteria (LLC), updated in 2018 with the integration of parametric mapping techniques, has significantly improved diagnostic sensitivity and specificity. This review details the definition, stages, and etiologies of myocarditis, exploring the diagnostic journey from early techniques to the modern multiparametric approach. It underscores the prognostic value of CMR findings and highlights challenging scenarios such as genetic cardiomyopathies that mimic myocarditis. It then discusses CMR patterns in specific conditions like cardiac sarcoidosis, amyloidosis, and immune checkpoint inhibitor-induced myocarditis. Finally, future perspectives for CMR in myocarditis are addressed. Full article

Objective: To evaluate the diagnostic yield and clinical impact of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with unexplained inflammation, fever, or suspected malignancy, and to assess its role across different rheumatologic subgroups. Methods: We retrospectively analyzed 280 patients who underwent PET/CT between 2010 and 2020 in a tertiary rheumatology center. Demographic, clinical, and laboratory data including erythrocyte sedimentation rate, C-reactive protein, and PET/CT indications were collected. PET/CT findings were categorized as inflammatory, neoplastic, or normal based on visual assessment and SUVmax. Final diagnoses were confirmed using clinical, histopathological, or follow-up data. Statistical analysis compared PET/CT results, inflammatory markers, and diagnostic outcomes among disease subgroups. Results: Of 280 patients (mean age 58 ± 15 years, 63.9% female), 72% had an established rheumatologic diagnosis prior to PET/CT. A new diagnosis, confirmed by predefined clinical, histopathological, or follow-up criteria, was established in 29.6% of patients, predominantly among those undergoing diagnostic evaluation for unexplained inflammation, including 40 rheumatologic and 43 non-rheumatologic conditions (22 malignancies). PET/CT led to therapeutic modification in 27.1% of all cases, based on multidisciplinary clinical decision-making. PET/CT demonstrated the highest diagnostic contribution in vasculitis, IgG4-related disease, and sarcoidosis. Median SUVmax was higher in malignancies than in inflammatory diseases [8.0 vs. 4.6, p < 0.05]. Lymphadenopathy was more frequent in non-rheumatologic and malignant conditions (p = 0.002). PET/CT findings showed variable but clinically relevant concordance with other imaging modalities. Conclusions: PET/CT provides supportive diagnostic and management insights in complex or atypical rheumatologic presentations. It demonstrated high yield in systemic inflammatory disorders and providing supportive information for malignancy exclusion in connective tissue diseases when interpreted alongside clinical and laboratory follow-up. Integration of PET/CT with clinical and laboratory data enhances diagnostic accuracy and supports patient-centered management in rheumatology. Full article

Background: Speckle-tracking echocardiography (STE) has been increasingly used to uncover subtle cardiac dysfunction in patients with extracardiac sarcoidosis (ECS) who show no clinical evidence of heart disease. However, prior investigations were mostly retrospective, methodologically heterogeneous, and focused primarily on left ventricular (LV) function. We conducted a prospective study to provide a broader evaluation of myocardial deformation across both ventricles and atria in ECS without fibrotic pulmonary involvement. Methods: Forty-one patients with ECS (mean age 57.4 ± 10.2 years; 58.5% male) and 30 age- and sex-matched controls without ECS and without known structural heart disease (58.5 ± 11.1 years; 53.3% male) were enrolled. All participants underwent conventional transthoracic echocardiography (TTE) supplemented by comprehensive STE analysis of ventricular and atrial function. Subclinical myocardial dysfunction was defined as LV global longitudinal strain (GLS) less negative than −20%, and potential predictors were analyzed. Results: Standard TTE did not show echocardiographic features suggestive of overt infiltrative cardiomyopathy but revealed higher E/average e′ ratios in the ECS group, suggesting subtle diastolic dysfunction. While traditional indices of biventricular systolic function remained preserved, STE demonstrated significant reductions in LV-GLS, LV global circumferential strain, right ventricular-GLS, and both left and right atrial reservoir strain. Multivariate analysis identified disease duration as the sole independent determinant of LV-GLS impairment (OR 2.26, 95%CI 1.10–4.65; p = 0.03). A disease duration of ≥4.5 years predicted abnormal GLS with 88% sensitivity and 75% specificity (AUC 0.89; 95%CI 0.76–1.00). Conclusions: ECS without fibrotic pulmonary involvement is associated with early impairment of biventricular and biatrial strain despite preserved conventional function. The extent of dysfunction correlates strongly with disease duration, underscoring the value of STE for early detection and monitoring. Full article

Dry eye disease (DED) has increasingly been linked to oxidative stress; however, the specific redox mechanisms underlying different clinical phenotypes remain incompletely understood. This study aimed to evaluate tear film oxidative stress profiles in patients with primary DED and sarcoidosis-associated DED (S-DED) by assessing lipid peroxidation, antioxidant enzyme activity, and total tear protein content, and to explore their relationship with clinical tear film dysfunction. Tear samples were analyzed for superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, as well as for malondialdehyde (MDA) and total protein levels, alongside standard clinical tests of tear film stability and secretion. Both DED groups exhibited significant oxidative alterations compared to controls, but with distinct redox signatures. Primary DED was characterized by markedly increased tear MDA levels, indicating predominant lipid peroxidation, whereas S-DED showed a more pronounced impairment of antioxidant defense, reflected by preserved or increased SOD activity in the context of significantly reduced GPx activity. Total tear protein levels were reduced in both groups, with evidence suggesting qualitative protein alterations in S-DED. The tear collection method significantly influenced the measured levels of several oxidative stress markers, underscoring the importance of sampling technique when interpreting tear-based redox profiles. Oxidative stress markers correlated with clinical measures of tear film dysfunction, supporting their physiological relevance. These findings demonstrate that DED encompasses heterogeneous oxidative stress mechanisms and that sarcoidosis acts as a modifier of ocular surface redox homeostasis. Distinct tear-based redox profiles differentiate primary from sarcoidosis-associated dry eye, highlighting the potential value of oxidative biomarkers for phenotyping DED beyond tear deficiency alone. Full article

Background: Ulcerative colitis (UC) and sarcoidosis are chronic inflammatory diseases that share immunological pathways but rarely coexist. The increasing use of biologic agents in inflammatory bowel disease (IBD) has raised concerns regarding paradoxical inflammatory manifestations, including sarcoidosis-like reactions. Case presentation: We report the case of a 63-year-old man with long-standing UC treated with vedolizumab who developed systemic sarcoidosis characterized by bilateral hilar lymphadenopathy, mediastinal and abdominal lymph node enlargement, pulmonary involvement, and erythema nodosum. Extensive diagnostic work-up, including imaging and histopathology, confirmed non-necrotizing granulomatous disease consistent with sarcoidosis, while alternative infectious, malignant, and drug-induced causes were excluded. Vedolizumab was temporarily discontinued, leading to UC relapse, and subsequently reintroduced with rapid clinical remission of UC. Discussion: Sarcoidosis remained clinically and radiologically stable despite vedolizumab re-initiation, suggesting a coincidental association rather than a direct causal relationship. This case highlights the diagnostic challenges and therapeutic dilemmas in patients with immune-mediated diseases receiving biologic therapy. Conclusion: The coexistence of UC and sarcoidosis during vedolizumab therapy is rare. Although causality cannot be established, our findings suggest that vedolizumab may be safely continued in selected patients under close multidisciplinary monitoring. Full article

Background: Psoriasis is a chronic systemic inflammatory disease with established extra-cutaneous manifestations. While the association between uveitis and spondyloarthritis (SpA)-related disorders is well recognized, the incident risk of uveitis among broader psoriasis populations remains inadequately defined due to methodological limitations and inconsistent findings across previous studies. We aimed to estimate the incidence of uveitis in a large, nationwide population-based cohort and identify specific clinical and treatment-related predictors of ocular inflammation. Methods: This retrospective cohort study utilised electronic health records from Clalit Health Services, Israel’s largest health maintenance organization (2002–2024). We identified 157,360 patients with dermatologist-confirmed psoriasis and 156,927 age- and sex-matched controls. The primary outcome was incident uveitis, with risk estimated using Cox proportional hazards models. Within the psoriasis cohort, multivariable logistic regression was employed to identify predictors of uveitis, ensuring appropriate temporal sequencing between psoriasis treatment exposure and outcome. Results: Over a median follow-up of 12.6 years, psoriasis was associated with a significantly higher risk of incident uveitis (adjusted Hazard Ratio [aHR] 1.80; 95% CI, 1.50–2.15). Stratified analysis revealed a graded risk pattern: mild psoriasis showed no increased risk (aHR 1.01; 95% CI, 0.91–1.13), whereas severe disease (aHR 1.59; 95% CI, 1.25–2.03) and concomitant SpA (aHR 2.21; 95% CI, 1.87–2.61) demonstrated markedly elevated risks. Within the psoriasis cohort, independent predictors included SpA, diabetes mellitus, systemic lupus erythematosus, and sarcoidosis. Exposure to biologics, particularly etanercept (OR 3.37; 95% CI, 2.42–4.54), was associated with higher odds of uveitis, potentially reflecting higher disease severity. Conclusions: Incident uveitis risk in psoriasis is primarily driven by the magnitude of systemic inflammatory burden, with the highest risk observed in severe disease and those with concomitant SpA. Clinicians should maintain heightened vigilance for ocular symptoms in these high-risk subgroups to ensure timely intervention. Full article

Background: Cardiac sarcoidosis (CS) is associated with potentially serious complications, including heart failure and life-threatening arrhythmias. The diagnosis and management of CS is multifaceted, requiring a multi-disciplinary team (MDT)-based approach. A new regional CS clinical service was established in Sussex County (UK) in January 2025. This service is based on a core of cardiologists working with a wider MDT, including specialists in pulmonary sarcoidosis, nuclear medicine and cardiac electrophysiology. This study assessed the clinical performance of this new service. Methods: Patients with suspected CS referred to the Sussex CS Service between January and December 2025 were included, as compared to a control cohort of patients referred for CS assessment before the service was conceived. Results: Of the 51 CS service referrals, 13 patients fulfilled the Heart Rhythm Society (HRS) criteria, all of whom were correctly diagnosed with CS, whilst only two out of seven HRS-positive control patients were correctly diagnosed. In the 38 HRS-negative CS service referrals, 8 patients (21%) were still given a clinical CS diagnosis compared to none in the HRS-negative controls. Of the 21 patients diagnosed with CS, 7 (33%) had active myocardial inflammation and 8 (38%) had LV systolic dysfunction. Where indicated, immunosuppressive and heart failure therapies were initiated in all patients. Eight CS patients (38%) underwent implantable cardioverter defibrillator implantation. No deaths or heart failure hospitalisations occurred within the first 11 months. Conclusions: An MDT-based CS service model can provide multi-faceted care to patients, without major short-term adverse outcomes. The service model replicability and long-term outcomes require further assessment. Full article

Tuberculosis and sarcoidosis can present with similar clinical and radiological features, especially intrathoracic lymphadenopathy, complicating differential diagnosis. This study explored the potential utility of QuantiFERON-TB Gold (QFT), serum High Mobility Group Box 1 protein (HMGB1), and microRNA-221 (miRNA-221) relative expression as biomarkers to aid in distinguishing tuberculosis-related intrathoracic lymphadenopathy (TBIL) from sarcoidosis-related intrathoracic lymphadenopathy (SAIL). The study included 27 patients with TBIL, 27 patients with SAIL, and 27 healthy controls. QFT results, serum HMGB1 levels, and miRNA-221 relative expression were measured and compared across groups using univariable and exploratory multivariable analyses. Significant differences were observed among the study groups for serum HMGB1 levels, miRNA-221 expression, and QFT results (p < 0.001). Both TBIL and SAIL patients had significantly higher HMGB1 levels compared with healthy controls, consistent with inflammatory activity. In contrast, miRNA-221 expression was significantly elevated in TBIL patients compared with both SAIL patients and controls. Exploratory analyses suggested a potential contribution of miRNA-221 to differentiating TBIL from SAIL, whereas the effects of HMGB1 and QFT were less pronounced after adjustment. The findings suggest that miRNA-221, alongside HMGB1 and QFT, may contribute to the differentiation of TBIL from SAIL, although validation in larger cohorts is necessary. Full article