Systemic inflammatory markers differentiate between orbital cellulitis and non-specific orbital inflammation.

PURPOSE: Bacterial orbital cellulitis (OC) and diffuse non-specific orbital inflammation (DNSOI) may be challenging to differentiate clinically. This study investigates the utility of systemic inflammatory markers, namely white cell count (WCC) and C-reactive protein (CRP), in differentiating between OC and DNSOI. METHODS: A single-centre retrospective study of patients diagnosed with OC or DNSOI, between 2003 to 2021, who had WCC and/or CRP obtained at presentation. The mean levels of these factors and the proportion of positivity were compared between OC and DNSOI. A receiver operating characteristic (ROC) analysis was conducted to calculate the specificity and sensitivity of WCC or CRP in each group. RESULTS: 49 patients were included in this study. The mean age was 56 ± 20 years, and 21 patients were females. 26 (53.1%) patients had OC, and 23 (46.9%) patients had DNSOI. Mean WCC for OC and DNSOI were 14.5 × 103/µL and 9.27 × 103/µL, respectively (P = 0.001). Mean CRP for OC and DNSOI were 104.4 mg/L and 10.0 mg/L, respectively (P < 0.001). The optimal CRP cut-off value of 20.2 mg/L demonstrated 90.9% sensitivity and 90.5% specificity (AUC = 0.946, P < 0.001) for differentiating between OC and DNSOI. CRP was more predictive of OC than WCC (P = 0.017). 7/26 (26.9%) OC patients with fever also had an elevated CRP, while 1/23 (4.3%) of DNSOI with fever had a normal CRP. CONCLUSIONS: An elevated WCC is suggestive of OC. However, a normal WCC can neither exclude nor differentiate between OC and DNSOI. CRP may be a more accurate predictor of OC compared to WCC.

Evaluation of Orbital Lymphoproliferative and Inflammatory Disorders by Gene Expression Analysis.

Non-specific orbital inflammation (NSOI) and IgG4-related orbital disease (IgG4-ROD) are often challenging to differentiate. Furthermore, it is still uncertain how chronic inflammation, such as IgG4-ROD, can lead to mucosa-associated lymphoid tissue (MALT) lymphoma. Therefore, we aimed to evaluate the diagnostic value of gene expression analysis to differentiate orbital autoimmune diseases and elucidate genetic overlaps. First, we established a database of NSOI, relapsing NSOI, IgG4-ROD and MALT lymphoma patients of our orbital center (2000−2019). In a consensus process, three typical patients of the above mentioned three groups (mean age 56.4 ± 17 years) at similar locations were selected. Afterwards, RNA was isolated using the RNeasy FFPE kit (Qiagen) from archived paraffin-embedded tissues. The RNA of these 12 patients were then subjected to gene expression analysis (NanoString nCounter®), including a total of 1364 target genes. The most significantly upregulated and downregulated genes were used for a machine learning algorithm to distinguish entities. This was possible with a high probability (p < 0.0001). Interestingly, gene expression patterns showed a characteristic overlap of lymphoma with IgG4-ROD and NSOI. In contrast, IgG4-ROD shared only altered expression of one gene regarding NSOI. To validate our potential biomarker genes, we isolated the RNA of a further 48 patients (24 NSOI, 11 IgG4-ROD, 13 lymphoma patients). Then, gene expression pattern analysis of the 35 identified target genes was performed using a custom-designed CodeSet to assess the prediction accuracy of the multi-parameter scoring algorithms. They showed high accuracy and good performance (AUC ROC: IgG4-ROD 0.81, MALT 0.82, NSOI 0.67). To conclude, genetic expression analysis has the potential for faster and more secure differentiation between NSOI and IgG4-ROD. MALT-lymphoma and IgG4-ROD showed more genetic similarities, which points towards progression to lymphoma.

Nonspecific orbital inflammation and thyroid eye disease, a rare comorbidity: report of two cases and review of literature.

BACKGROUND: To present the very rare comorbidity of developing non-specific orbital inflammation (NSOI) in two patients with histories of definite thyroid eye disease (TED). CASE PRESENTATION: Both patients complained of new-onset progressive proptosis although their thyroid disease was controlled and computed tomography scan revealed an intraorbital inflammatory mass. The pathological assessment indicated that both patients had developed fibrosing NSOI. Therefore, intravenous corticosteroids were administered. The mass regressed and the amount of proptosis was decreased in both patients. CONCLUSIONS: We reviewed all related cases in the literature and extracted their clinical and radiological characteristics for this paper. Ophthalmologists should consider TED and NSOI in patients with a new-onset complaint of proptosis. Despite rare comorbidity of TED and NSOI, it should be considered especially in patients with refractory proptosis, and lead to its further evaluation and prompt management.

Elucidating the multifaceted roles of GPR146 in non-specific orbital inflammation: a concerted analytical approach through the prisms of bioinformatics and machine learning.

Background: Non-specific Orbital Inflammation (NSOI) is a chronic idiopathic condition marked by extensive polymorphic lymphoid infiltration in the orbital area. The integration of metabolic and immune pathways suggests potential therapeutic roles for C-peptide and G protein-coupled receptor 146 (GPR146) in diabetes and its sequelae. However, the specific mechanisms through which GPR146 modulates immune responses remain poorly understood. Furthermore, the utility of GPR146 as a diagnostic or prognostic marker for NSOI has not been conclusively demonstrated. Methods: We adopted a comprehensive analytical strategy, merging differentially expressed genes (DEGs) from the Gene Expression Omnibus (GEO) datasets GSE58331 and GSE105149 with immune-related genes from the ImmPort database. Our methodology combined LASSO regression and support vector machine-recursive feature elimination (SVM-RFE) for feature selection, followed by Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) to explore gene sets co-expressed with GPR146, identifying a significant enrichment in immune-related pathways. The tumor microenvironment's immune composition was quantified using the CIBERSORT algorithm and the ESTIMATE method, which confirmed a positive correlation between GPR146 expression and immune cell infiltration. Validation of GPR146 expression was performed using the GSE58331 dataset. Results: Analysis identified 113 DEGs associated with GPR146, with a significant subset showing distinct expression patterns. Using LASSO and SVM-RFE, we pinpointed 15 key hub genes. Functionally, these genes and GPR146 were predominantly linked to receptor ligand activity, immune receptor activity, and cytokine-mediated signaling. Specific immune cells, such as memory B cells, M2 macrophages, resting mast cells, monocytes, activated NK cells, plasma cells, and CD8+ T cells, were positively associated with GPR146 expression. In contrast, M0 macrophages, naive B cells, M1 macrophages, activated mast cells, activated memory CD4+ T cells, naive CD4+ T cells, and gamma delta T cells showed inverse correlations. Notably, our findings underscore the potential diagnostic relevance of GPR146 in distinguishing NSOI. Conclusion: Our study elucidates the immunological signatures associated with GPR146 in the context of NSOI, highlighting its prognostic and diagnostic potential. These insights pave the way for GPR146 to be a novel biomarker for monitoring the progression of NSOI, providing a foundation for future therapeutic strategies targeting immune-metabolic pathways.

IgG4-related orbital disease. / Enfermedad orbitaria relacionada con Ig-G4.

CASE REPORT: The case is presented of a 64-year-old woman with bilateral palpebral swelling and dacryoadenitis, exophthalmos, and a history of chronic rhinitis and asthma. An increase in serum IgG4 was observed, and an incisional biopsy of lacrimal glands was performed, which showed fibrosis and a lymphoplasmacytic infiltrate with IgG4 producing cells. DISCUSSION: Orbital involvement in IgG4-related disease is frequent. Bilateral dacryoadenitis is the most common manifestation. Histopathology is essential for the diagnosis and to exclude malignancy.