Idiopathic granulomatous mastitis: clinical, histopathological, and radiological characteristics and management approaches.

Idiopathic Granulomatous Mastitis (IGM) is an infrequent, benign breast disease that primarily affects women during their childbearing years and can be mistaken for breast cancer. This study aimed to review the clinical, radiological, and histopathological findings of patients with IGM in addition to management and outcome. Retrospective cross-sectional study of biopsy-confirmed IGM at an academic medical center and a private hospital in Amman, Jordan. Fifty-four patients were included, with a mean age of 37.0 ± 9.04 years, mostly presenting with a breast lump (n = 52, 96.3%) and breast pain (n = 45 patients, 84.9%). Approximately half of the patients (51.9%) were parous, and 50% had breastfed for an average duration of 30.37 ± 22.38 months. Most of the patients had either solitary or multiple abscesses on breast ultrasound. Histopathological analysis (n = 35) showed mostly either moderate inflammation (n = 16, 45.7%) or severe inflammation (n = 14, 40%). Two-thirds of the patients underwent surgical interventions at the time of diagnosis, mostly incision and drainage (n = 16, 29%) or surgical excision (n = 7, 13%), and no mastectomies were performed. The most common medical treatment included a combination of antibiotics, corticosteroids, and methotrexate (n = 21, 38.8%). After follow-up, 31 patients remained in remission, 3 experienced relapses, and 3 had a chronic course. The use of corticosteroids was significantly associated with remission (p = 0.035). The presentation and demographics of IGM patients in Jordan were consistent with the existing literature. Prospective research is needed to explore different treatment options and disease outcomes.

Detection of early phenotype cardiac sarcoidosis by cardiovascular magnetic resonance.

PURPOSE OF REVIEW: Cardiac sarcoidosis has high prevalence in sarcoidosis patients and contributes to significant morbidity and mortality. Early detection of cardiac sarcoidosis is essential to improving patients' symptoms and cardiovascular outcomes. RECENT FINDINGS: Cardiovascular magnetic resonance imaging (CMR) is an excellent diagnostic modality for cardiac sarcoidosis. However, early phenotypes of cardiac sarcoidosis have more mild imaging phenotypes. These mild and sometimes subtle imaging phenotypes of cardiac sarcoidosis have lower diagnostic sensitivity and specificity for cardiac sarcoidosis by CMR when compared with more severe imaging phenotypes of cardiac sarcoidosis. In addition, many sarcoidosis patient cohorts frequently have heterogenous potential alternative etiologies for mild myocardial disease detected by mild late gadolinium enhancement (LGE) findings. In early phenotype cardiac sarcoidosis, analysis of the LGE pattern and location can improve the diagnostic specificity of these mild LGE findings. SUMMARY: The current review focuses on the current strengths and challenges in CMR detection of early phenotypes of cardiac sarcoidosis by the LGE technique.

COVID-19 infection in patients with sarcoidosis: susceptibility and clinical outcomes.

PURPOSE OF REVIEW: Patients with sarcoidosis may be at higher risk of coronavirus disease-19 (COVID-19) as over 90% of the patients have pulmonary involvement and many are treated with immunosuppressive agents. This review will summarize the current literature regarding sarcoidosis and COVID-19, with a particular focus on susceptibility, clinical outcomes, management, and approach to vaccination. RECENT FINDINGS: Data about COVID-19 and sarcoidosis include a number of case series and reports, cohort studies, and registries. Literature is not conclusive whether patients with sarcoidosis have increased susceptibility to COVID-19. Patients with moderate to severe impaired pulmonary function may be at increased risk of adverse outcomes and mortality. Whether immunosuppressive medication increases risk of COVID-19 severity or affects vaccination response is not yet clear. Novel approaches, such as telemedicine and home monitoring programs, are promising to ensure continuity of care for patients with sarcoidosis during the COVID-19 pandemic. SUMMARY: Current evidence about the risk and clinical outcomes of COVID-19 infection in patient with sarcoidosis, is mainly extrapolated from other immune-mediated diseases. Hence, further research that focuses on the sarcoidosis population is warranted.

Sarcoidosis and autoimmunity.

PURPOSE OF REVIEW: Sarcoidosis is a poorly understood multisystem granulomatous disease that frequently involves the lungs but can affect any organ system. In this review, we summarize recent developments in the understanding of the immune dysregulation seen in sarcoidosis and propose a new expanded definition of human autoimmunity in sarcoidosis, and the implications it would have on treating sarcoidosis with targeted immunotherapy regimens in the future. RECENT FINDINGS: Sarcoidosis has been linked to infectious organisms like Mycobacterium and Cutibacterium, and certain manifestations of sarcoidosis have been linked to specific HLA alleles, but the overall pathogenesis remains uncertain. Sarcoidosis patients have similar patterns of cellular immune dysregulation seen in other autoimmune diseases like rheumatoid arthritis, and recent large-scale population studies show that sarcoidosis frequently presents with other autoimmune diseases. SUMMARY: Advancements in the understanding of sarcoidosis support its consideration as an autoimmune disease. Sarcoidosis patients carry a higher risk of comorbid autoimmune conditions which offers an excellent opportunity to further understand autoimmunity and explore biologic therapies in sarcoidosis treatment, and furthermore will better targeted immunotherapy regimens for sarcoidosis patients in the future.

FDG PET-CT findings of extra-thoracic sarcoid are associated with cardiac sarcoid: A rationale for using FGD PET-CT for cardiac sarcoid evaluation.

PURPOSE: This retrospective study investigates the relationship between cardiac and extra-thoracic sarcoid findings on FDG PET-CT using a 72-hour pretest high-fat, high-protein, and very low-carbohydrate (HFHPVLC) diet. PATIENTS AND METHODS: A total of 196 consecutive FDG PET-CT scans with 72-hour HFHPVLC diet preparation were performed between December 2014 and December 2015 in known sarcoid patients. Of these scans, 5 were excluded for non-adherence to diet preparation or underlying cancer. Cardiac and extra-thoracic sarcoid lesions were categorized and measured for radiotracer uptake. RESULTS: A total of 188 patients had 191 eligible FDG PET/CT scans (3 follow-up scans), of which there were 20 (10%) positive, 6 indeterminate (3%), and 165 (86%) negative for CS. Among the 20 scans positive for CS, 8 (40%) had findings of both cardiac and extra-thoracic sarcoid. CONCLUSION: Our study shows that 40% of CS patients also have FDG PET-CT findings of extra-thoracic sarcoid. This makes an intriguing case for FDG PET-CT use with pretest diet prep over cardiac MRI (CMR) for cardiac sarcoid evaluation, given that CMR is likely to overlook these extra-thoracic sites of disease.

Improved detection of myocardial damage in sarcoidosis using longitudinal strain in patients with preserved left ventricular ejection fraction.

BACKGROUND: Cardiac infiltration is an important cause of death in sarcoidosis. Transthoracic echocardiography (TTE) has limited sensitivity for the detection of cardiac sarcoidosis (CS). Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) is used to diagnose CS but has limitations of cost and availability. We sought to determine whether TTE-derived global longitudinal strain (GLS) may be used to identify individuals with CS, despite preserved left ventricular ejection fraction (LVEF), and whether abnormal GLS is associated with major cardiovascular events (MCE). METHODS: We studied 31 patients with biopsy-proven extra-cardiac sarcoidosis, LVEF>50% and LGE on CMR (CS+ group), and 31 patients without LGE (CS- group), matched by age, sex, and severity of lung disease. GLS was measured using vendor-independent speckle tracking software. Parameters of left and right ventricular systolic and diastolic function were also studied. Receiver-operating characteristic curves were used to identify GLS cutoff for CS detection, and Kaplan-Meier plots to determine the ability of GLS to predict MCE. RESULTS: LGE was associated with reduced GLS (-19.6±1.9% in CS- vs -14.7±2.4% in CS+, P<.01) and with reduced E/A ratio (1.1±0.3 vs 0.9±0.3, respectively, P =.01). No differences were noted in other TTE parameters. GLS magnitude inversely correlated with LGE burden (r=-.59). GLS cutoff of -17% showed sensitivity and specificity 94% for detecting CS. Patients who experienced MCE had worse GLS than those who did not (-13.4±0.9% vs -17.7±0.4%, P=.0003). CONCLUSIONS: CS is associated with significantly reduced GLS in the presence of preserved LVEF. GLS measurements may become part of the TTE study performed to screen for CS.

Refractory pulmonary sarcoidosis - proposal of a definition and recommendations for the diagnostic and therapeutic approach.

Patients with sarcoidosis undergo spontaneous remission or may be effectively controlled with glucocorticoids alone in many cases. Progressive and refractory pulmonary sarcoidoisis constitute more than 10% of patients seen at specialized centers. Pulmonary fibrosis and associated complications, such as infections and pulmonary hypertension are leading causes of mortality. No universal definition of refractoriness exists, we therefore propose classifying patients as having refractory disease when the following criteria are fulfilled: (1) progressive disease despite at least 10 mg of prednisolone or equivalent for at least three months and need for additional disease-modifying anti-sarcoid drugs due to lack of efficacy, drug toxicity or intolerability and (2) treatment started for significant impairment of life due to progressive pulmonary symptoms. Both criteria should be fulfilled. Treatment options in addition to or instead of glucocorticoids for these patients include second- (methotrexate, azathioprine, leflunomide) and third-line agents (infliximab, adalimumab). Other immunmodulating agents can be used, but the evidence is very limited. Newer agents with anti-fibrotic properties, such as pirfenidone or nintedanib, might hold promise also for the pulmonary fibrosis seen in sarcoidosis. Treating physicians have to actively look for potentially treatable complications, such as pulmonary hypertension, cardiac disease or infections before patients should be classified as treatment-refractory. Ultimately, lung transplantation has to be considered as treatment option for patients not responding to medical therapy. In this review, we aim to propose a new definition of refractoriness, describe the associated clinical features and suggest the therapeutic approach.

Metabolic reprogramming by Syntenin-1 directs RA FLS and endothelial cell-mediated inflammation and angiogenesis.

A novel rheumatoid arthritis (RA) synovial fluid protein, Syntenin-1, and its receptor, Syndecan-1 (SDC-1), are colocalized on RA synovial tissue endothelial cells and fibroblast-like synoviocytes (FLS). Syntenin-1 exacerbates the inflammatory landscape of endothelial cells and RA FLS by upregulating transcription of IRF1/5/7/9, IL-1ß, IL-6, and CCL2 through SDC-1 ligation and HIF1α, or mTOR activation. Mechanistically, Syntenin-1 orchestrates RA FLS and endothelial cell invasion via SDC-1 and/or mTOR signaling. In Syntenin-1 reprogrammed endothelial cells, the dynamic expression of metabolic intermediates coincides with escalated glycolysis along with unchanged oxidative factors, AMPK, PGC-1α, citrate, and inactive oxidative phosphorylation. Conversely, RA FLS rewired by Syntenin-1 displayed a modest glycolytic-ATP accompanied by a robust mitochondrial-ATP capacity. The enriched mitochondrial-ATP detected in Syntenin-1 reprogrammed RA FLS was coupled with mitochondrial fusion and fission recapitulated by escalated Mitofusin-2 and DRP1 expression. We found that VEGFR1/2 and Notch1 networks are responsible for the crosstalk between Syntenin-1 rewired endothelial cells and RA FLS, which are also represented in RA explants. Similar to RA explants, morphological and transcriptome studies authenticated the importance of VEGFR1/2, Notch1, RAPTOR, and HIF1α pathways in Syntenin-1 arthritic mice and their obstruction in SDC-1 deficient animals. Consistently, dysregulation of SDC-1, mTOR, and HIF1α negated Syntenin-1 inflammatory phenotype in RA explants, while inhibition of HIF1α impaired synovial angiogenic imprint amplified by Syntenin-1. In conclusion, since the current therapies are ineffective on Syntenin-1 and SDC-1 expression in RA synovial tissue and blood, targeting this pathway and its interconnected metabolic intermediates may provide a novel therapeutic strategy.

Established and experimental medical therapy of pulmonary sarcoidosis.

The treatment options for pulmonary sarcoidosis have increased over the past 10 years. As new treatments have been introduced, the best way to assess and compare treatments remains unknown. The goal of this review is to discuss the standard treatments for pulmonary sarcoidosis, including glucocorticoids, and cytotoxic agents, such as methotrexate, azathioprine and leflunomide, and compare them to the newer biological agents, such as infliximab and adalimumab. We also discuss some novel treatments which are currently being evaluated. To compare these different regimens, we look at the measures used to assess response. These include pulmonary function, chest imaging, steroid sparing potential and, more recently, improvements in quality of life measures. While there is, as yet, no standard assessment for response, there is a growing consensus that response to treatment may include improvement of one or more of the following: forced vital capacity, chest imaging and steroid sparing. Several drugs used for pulmonary sarcoidosis have demonstrated improvement in one or more of these measures.