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.

Circulating cytokines in sarcoidosis: phenotype-specific alterations for fibrotic and non-fibrotic pulmonary disease.

AIMS: Sarcoidosis is a granulomatous disease of unknown etiology marked by tremendous clinical heterogeneity. Many patients enter remission with good long-term outcomes. Yet, chronic disease is not uncommon, and this important phenotype remains understudied. Identified alterations in local and circulating cytokines--specifically targeted for study, and often in the acute phase of disease--have informed our growing understanding of the immunopathogenesis of sarcoidosis. Our aim was to evaluate a broad panel of circulating cytokines in patients with chronic sarcoidosis. Among those with chronic disease, pulmonary fibrosis occurs in only a subset. To gain more insight into the determinants of the fibrotic response, we also determined if the phenotypes of fibrotic and non-fibrotic pulmonary sarcoidosis have distinct cytokine profiles. RESULTS: In patients with sarcoidosis compared to controls, IL-5 was decreased, and IL-7 was increased. Both of these comparisons withstood rigorous statistical correction for multiple comparisons. GM-CSF met a nominal level of significance. We also detected an effect of phenotype, where IL-5 was significantly decreased in non-fibrotic compared to fibrotic pulmonary sarcoidosis, and compared to controls. Compared to controls, there was a trend towards a significant increase in IL-7 in fibrotic, but not in non-fibrotic pulmonary sarcoidosis. In contrast, compared to controls, there was a trend towards a significant increase in GM-CSF in non-fibrotic, but not in fibrotic pulmonary sarcoidosis. CONCLUSIONS: In a comprehensive evaluation of circulating cytokines in sarcoidosis, we found IL-5, IL-7, and GM-CSF to be altered. These findings provide a window into the immunopathogenesis of sarcoidosis. IL-7 is a novel sarcoidosis cytokine and, as a master regulator of lymphocytes, is an attractive target for further studies. By observing an effect of phenotype upon cytokine patterns, we also identify specific immune alterations which may contribute to clinical heterogeneity.

Nonsteroidal therapy of sarcoidosis.

PURPOSE OF REVIEW: None of the medications used in clinical practice to treat sarcoidosis have been approved by the regulatory authorities. Understanding how to use disease-modifying antisarcoid drugs, however, is essential for physicians treating patients with sarcoidosis. This review summarizes the recent studies of medications used for sarcoidosis with a focus on nonsteroidal therapies. Studies from 2006 to 2013 were considered for review to update clinicians on the most relevant literature published over the last few years. RECENT FINDINGS: Several recently published pieces of evidence have helped expand our ability to more appropriately sequence second-line and third-line therapies for sarcoidosis. For instance, methotrexate and azathioprine may be useful and well tolerated medications as second-line treatment. Mycophenolate mofetil might have a role in neurosarcoidosis. TNF-α blockers and other biologics seem to be well tolerated medications for the most severely affected patients. SUMMARY: Corticosteroids remain the first-line therapy for sarcoidosis as many patients never require treatment or only necessitate a short treatment duration. Second-line and third-line therapies described in this article should be used in patients with progressive or refractory disease or when life-threatening complications are evident at the time of presentation.

Multinational evidence-based World Association of Sarcoidosis and Other Granulomatous Disorders recommendations for the use of methotrexate in sarcoidosis: integrating systematic literature research and expert opinion of sarcoidologists worldwide.

PURPOSE OF REVIEW: Although glucocorticosteroids are considered the first-line treatment in sarcoidosis, refractory cases require alternatives, such as methotrexate (MTX). The aim of this study was to develop, on behalf of the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG), multinational evidence-based recommendations for the use of MTX in sarcoidosis for routine clinical practice. RECENT FINDINGS: A systematic literature search was conducted and combined with the opinions of sarcoidosis experts worldwide to formulate the recommendations. An online survey concerning 10 clinical questions was sent through the WASOG newsletter to sarcoidosis experts. Agreement about the recommendations amongst the world's leading sarcoidologists was evaluated. A total of 237 articles were identified, 43 of which were included. Randomized controlled trial evidence supporting the use of MTX in sarcoidosis was limited. Forty-five per cent (113 of 250) of the sarcoidosis experts contacted completed the survey (Europe 55%, North America 26% and Asia 12%). Ten recommendations were formulated concerning the indications for use, starting dose, folic acid, work-up, contraindications, monitoring, administration options in case of adverse gastrointestinal effects, hepatotoxicity, long-term safety and use during pregnancy and breast feeding. SUMMARY: Ten multinational evidence-based recommendations for the use of MTX in sarcoidosis were developed, which are supported by the world's foremost sarcoidosis experts.

Pitfalls in the Diagnosis and Management of an Unusual Presentation of Clinically Amyopathic Dermatomyositis: A Case Report Written With the Assistance of ChatGPT.

Clinically amyopathic dermatomyositis (CADM) is a rare form of dermatomyositis. Patients with this condition present with the typical skin findings of dermatomyositis but lack the characteristic muscle weakness associated with dermatomyositis. This case presentation highlights the unusual clinical manifestation of CADM in a 49-year-old Vietnamese female. The patient initially presented with persistent hyperpigmented plaques on her hands, which did not respond to the standard treatment for atopic dermatitis. The patient later developed respiratory failure and lung fibrosis in Vietnam. This case underscores the challenges in diagnosing and managing CADM, particularly in patients with atypical presentations, and emphasizes the difficulties in managing such cases of CADM in the community setting.

Treatment of Periorbital Edema in a Patient With Systemic Lupus Erythematosus During Pregnancy: A Case Report Written With the Assistance of ChatGPT.

Systemic lupus erythematosus (SLE) is an autoimmune disease that has a wide range of manifestations and can affect nearly every organ system. Skin manifestations are a common finding in SLE. They are often photosensitive and can be exacerbated by exposure to ultraviolet light. Here, we discuss the case of a 34-year-old African American woman who presented with periorbital edema while 12 weeks pregnant. This case highlights the importance of avoiding sun exposure in patients with SLE and the challenge of treating SLE during pregnancy.

Corrigendum: Reproducibility and rigor in rheumatology research.

[This corrects the article DOI: 10.3389/fmed.2022.1073551.].

Initial behaviors and attitudes towards the COVID-19 vaccine in sarcoidosis patients: results of a self-reporting questionnaire.

BACKGROUND: Individuals with self-declared sarcoidosis are at increased risk of COVID-19 related morbidity and mortality for which vaccination can be lifesaving. Despite this, vaccine hesitancy remains a large barrier to global acceptance of vaccination against COVID-19. We aimed to identify individuals with sarcoidosis who had and had not been vaccinated against COVID-19 vaccine to 1) establish a safety profile of COVID-19 vaccination in those with sarcoidosis and 2) to elucidate factors that contribute to COVID-19 vaccine hesitancy. METHODS: A questionnaire inquiring about COVID-19 vaccination status, vaccination side effects, and willingness for future vaccination was distributed from December 2020 to May 2021 to individuals with sarcoidosis living in the US and European countries. Details regarding sarcoidosis manifestations and treatment were solicited. Vaccine attitudes were classified as pro or anti-COVID-19 vaccination for subgroup analysis. RESULTS: At the time of questionnaire administration, 42% of respondents had already received a COVID-19 vaccination, most of whom either denied side effects or reported a local reaction only. Those off sarcoidosis therapy were more likely to report systemic side effects. Among subjects who had not yet received a COVID-19 vaccine, 27% of individuals reported they would not receive one once available. Reasons against vaccination were overwhelmingly related to the lack of confidence in vaccine safety and/or efficacy and less related to concerns associated with convenience or complacency. Black individuals, women, and younger adults were more likely to decline vaccination. CONCLUSIONS: Among individuals with sarcoidosis, COVID-19 vaccination is well-accepted and well-tolerated. Subjects on sarcoidosis therapy reported significantly less vaccination side effects, and thus the correlation between side effects, vaccine type, and vaccine efficacy requires further investigation. Strategies to improve vaccination should focus on improving knowledge and education regarding vaccine safety and efficacy, as well as targeting sources of misinformation, particularly in young, black, and female subpopulations.

Trimer IgG and neutralising antibody response to COVID-19 mRNA vaccination in individuals with sarcoidosis.

Background: Individuals with sarcoidosis are at higher risk for infection owing to underlying disease pathogenesis and need for immunosuppressive treatment. Current knowledge as to how subjects with sarcoidosis respond to different forms of vaccination is limited. We examined quantitative and functional antibody response to COVID-19 vaccination in infection-naive subjects with and without sarcoidosis. Methods: Our prospective cohort study recruited 14 subjects with biopsy-proven sarcoidosis and 27 age-sex matched controls who underwent a two-shot series of the BNT162b2 mRNA vaccine at the University of Illinois at Chicago. Baseline, 4-week and 6-month trimer spike protein IgG and neutralising antibody (nAb) titres were assessed. Correlation and multivariate regression analysis was conducted. Results: Sarcoidosis subjects had a significant increase in short-term antibody production to a level comparable to controls; however, IgG titres significantly declined back to baseline levels by 6 months. Corresponding neutralising assays revealed robust nAb titres in sarcoidosis subjects that persisted at 6 months. A significant and strong correlation between IgG and nAb titres across all time points was observed in the control group. However within the sarcoidosis group, a significant but weak correlation between antibody levels was found. Overall, IgG levels were poor predictors of nAb titres at short- or long-term time points. Conclusions: Sarcoidosis subjects exhibit nAb induced by the BNT162b2 mRNA SARS-CoV-2 vaccine at levels comparable to controls that persists at 6 months indicating conferred immunity. Trimer IgG levels are poor predictors of nAb in subjects with sarcoidosis. Studies of further antibody immunoglobulins and subtypes warrant investigation.

Efzofitimod for the Treatment of Pulmonary Sarcoidosis.

BACKGROUND: Pulmonary sarcoidosis is characterized by the accumulation of immune cells that form granulomas affecting the lungs. Efzofitimod (ATYR1923), a novel immunomodulator, selectively binds neuropilin 2, which is upregulated on immune cells in response to lung inflammation. RESEARCH QUESTION: What is the tolerability, safety, and effect on outcomes of efzofitimod in pulmonary sarcoidosis? STUDY DESIGN AND METHODS: In this randomized, double-blind, placebo-controlled study evaluating multiple ascending doses of efzofitimod administered intravenously every 4 weeks for 24 weeks, randomized patients (2:1) underwent a steroid taper to 5 mg/d by week 8 or < 5 mg/d after week 16. The primary end point was the incidence of adverse events (AEs); secondary end points included steroid reduction, change in lung function, and patient-reported outcomes on health-related quality-of-life scales. RESULTS: Thirty-seven patients received at least one dose of study medication. Efzofitimod was well tolerated at all doses, with no new or unexpected AEs and no dose-dependent AE incidence. Average daily steroid doses through end of study were 6.8 mg, 6.5 mg, and 5.6 mg for the 1 mg/kg, 3 mg/kg, and 5 mg/kg groups compared with 7.2 mg for placebo, resulting in a baseline-adjusted relative steroid reduction of 5%, 9%, and 22%, respectively. Clinically meaningful improvements were achieved across several patient-reported outcomes, several of which reached statistical significance in the 5 mg/kg dose arm. A dose-dependent but nonsignificant trend toward improved lung function also was observed for 3 and 5 mg/kg. INTERPRETATION: Efzofitimod was safe and well tolerated and was associated with dose-dependent improvements of several clinically relevant end points compared with placebo. The results of this study support further evaluation of efzofitimod in pulmonary sarcoidosis. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03824392; URL: www. CLINICALTRIALS: gov.