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Sarcoidosis is a disease characterized by immunological granuloma formation in various organs. Cutaneous manifestations occur in about 25% of patients with rare cases showing ulcerative sarcoidosis, that can be debilitating if not treated promptly. This article presents a patient with isolated ulcerative sarcoidosis and reviews existing literature. A 44-year-old woman presented with a non-healing ulcer on her right gluteal area. A skin biopsy confirmed sarcoidosis with non-necrotizing granulomas. Systemic involvement of sarcoidosis was ruled out. Treatment involved topical corticosteroids and intralesional corticosteroid injections, resulting in complete healing. This case emphasizes the importance of considering ulcerative sarcoidosis in non-healing wounds and the efficacy of corticosteroid treatment.

PURPOSE: This study aims to explore the potential subgroups of sarcoidosis-associated uveitis (SAU) within a multicenter cohort of uveitis participants. DESIGN: Cross-sectional study. PARTICIPANTS: A cohort of 826 uveitis patients from a uveitis registry from 19 clinical centers in 12 countries between January 2011 and April 2015. METHODS: We employed a latent class analysis (LCA) incorporating recommended tests and clinical signs from the revised International Workshop on Ocular Sarcoidosis (IWOS) to identify potential SAU subgroups within the multicenter uveitis cohort. Additionally, we assessed the performance of the individual tests and clinical signs in classifying the potential subclasses. MAIN OUTCOME MEASURES: Latent subtypes of SAU. RESULTS: Among 826 participants included in this analysis, the 2-class LCA model provided a best fit, with the lowest Bayesian information criteria of 7218.7 and an entropy of 0.715. One class, consisting of 548 participants, represented the non-SAU, whereas the second class, comprised of 278 participants, was most representative of SAU. Snowballs/string of pearls vitreous opacities had the best test performance for classification, followed by bilaterality and bilateral hilar lymphadenopathy (BHL). The combination of 4 tests with the highest classification importance, including snowballs/string of pearls vitreous opacities, periphlebitis and/or macroaneurysm, bilaterality, and BHL, demonstrated a sensitivity of 84.8% and a specificity of 95.4% in classifying the SAU subtypes. In the exploratory analysis of the 3-class LCA model, which had comparable fit indices as the 2-class model, we identified a candidate non-SAU subtype, candidate SAU subtype with pulmonary involvement, and a candidate SAU with less pulmonary involvement. CONCLUSIONS: Latent class modeling, incorporating tests and clinical signs from the revised IWOS criteria, effectively identified a subset of participants with clinical features indicative of SAU. Though the sensitivity of individual ocular signs or tests was not perfect, using a combination of tests provided a satisfactory performance in classifying the SAU subclasses identified by the 2-class LCA model. Notably, the classes identified by the 3-class LCA model, including a non-SAU subtype, an SAU subtype with pulmonary involvement, and an SAU subtype with less pulmonary involvement, may have potential implication for clinical practice, and hence should be validated in further research. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

PurposeMethodsResultsConclusionTo review the clinical presentation and diagnostic workup of patients presenting with ocular sarcoidosis as initial manifestation of the disease and identify risk factors for disease recurrence.All cases of sarcoidosis followed in our departments of Ophthalmology and Internal Medicine were retrospectively reviewed. Among 177 patients, 50 had ocular sarcoidosis as initial presentation of the disease. Clinical, biological, radiological, and treatment data were collected. Logistic regression analysis was conducted to identify risk factors for recurrence.Mean age of patients was 51 years, with an equal M/F ratio. Bilateral ocular involvement was present in 86% of cases, with granulomatous panuveitis being the most common manifestation (48%). Two-thirds of patients had extraocular symptoms related to the disease, mostly fatigue. The most frequently involved extraocular site was the supradiaphragmatic lymph nodes, identified in 84% of cases. CRP was normal in 68% of patients, while ACE and lysozyme were elevated in 19% and 64% of cases, respectively. Histopathological confirmation was obtained in 68% of patients. Female sex (odds ratio [OR] 6.66, 95% confidence interval [CI] 1.50–40.40, p = 0.021) and granulomatous panuveitis (OR 7.23, 95% CI 1.70–40.99, p = 0.013) were identified as significant risk factors for disease recurrence.Ocular sarcoidosis is a common initial presentation of systemic sarcoidosis. Diagnosis should be suspected in the presence of bilateral granulomatous panuveitis. Chest CT scan or 18F-FDG PET/CT is mandatory for systemic workup and biopsy is necessary for definite diagnosis. Female sex and a panuveitis presentation are significantly associated with disease recurrence. [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 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]

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]

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]

Sarcoidosis is a multiorgan granulomatous disease that lacks diagnostic biomarkers and targeted treatments. Using blood and skin from patients with sarcoid and non-sarcoid skin granulomas, we discovered that skin granulomas from different diseases exhibit unique immune cell recruitment and molecular signatures. Sarcoid skin granulomas were specifically enriched for type 1 innate lymphoid cells (ILC1s) and B cells and exhibited molecular programs associated with formation of mature tertiary lymphoid structures (TLSs), including increased CXCL12/CXCR4 signaling. Lung sarcoidosis granulomas also displayed similar immune cell recruitment. Thus, granuloma formation was not a generic molecular response. In addition to tissue-specific effects, patients with sarcoidosis exhibited an 8-fold increase in circulating ILC1s, which correlated with treatment status. Multiple immune cell types induced CXCL12/CXCR4 signaling in sarcoidosis, including Th1 T cells, macrophages, and ILCs. Mechanistically, CXCR4 inhibition reduced sarcoidosis-activated immune cell migration, and targeting CXCR4 or total ILCs attenuated granuloma formation in a noninfectious mouse model. Taken together, our results show that ILC1s are a tissue and circulating biomarker that distinguishes sarcoidosis from other skin granulomatous diseases. Repurposing existing CXCR4 inhibitors may offer a new targeted treatment for this devastating disease. [ABSTRACT FROM AUTHOR]