Cutaneous Crohn disease presenting as "knife-edged" ulcers: a case report.

BACKGROUND: CCD presents as non-caseating granulomas within the skin at a site distant from the GI tract. CCD is a debilitating extraintestinal sequela of CD that can sometimes precede its GI manifestations. In the absence of GI symptoms, the histopathologic and clinical features of CCD can present as a variety of inflammatory skin conditions that can range from ruptured follicle-associated granulomas to cutaneous ulcerations. While a variety of therapeutic options for patients with CCD and concurrent luminal CD have been described in the literature, there is no standard treatment algorithm for the management of refractory CCD with limited or covert GI involvement. CASE REPORT: The authors discuss the case of a 33-year-old female who presented to the wound care clinic with multiple "knife-edged" cutaneous ulcerations involving the intertriginous spaces, found to be consistent with CCD. Her original cutaneous symptoms and diagnosis manifested with minimal GI involvement and responded to IVIG treatment. CONCLUSIONS: This case supports the inclusion of CCD in the differential diagnosis in patients with knife-edged granulomatous skin lesions in intertriginous locations. This clinical condition may present in the setting of no or limited GI symptoms. The management of CCD and a proposed treatment algorithm are also presented.

From Acute Infection to Prolonged Health Consequences: Understanding Health Disparities and Economic Implications in Long COVID Worldwide.

The COVID-19 pandemic has resulted in a growing number of patients experiencing persistent symptoms and physiological changes after recovering from acute SARS-CoV-2 infection, known as Long COVID. Long COVID is characterized by recurring symptoms and inflammation across multiple organ systems. Diagnosis can be challenging, influenced by factors like demographics, comorbidities, and immune responses. Long COVID impacts various organ systems and can have neuropsychological effects. Health disparities, particularly related to race, contribute to a higher burden of infection and ongoing symptoms in minority populations. Managing Long COVID entails addressing a spectrum of symptoms that encompass physical, cognitive, and psychological aspects. The recovery period for patients with Long COVID can vary significantly, influenced by factors like the severity of the disease, hospitalization, comorbidities, and age. Currently, there are no universally effective treatments, although certain interventions show promise, necessitating further research. Self-management and rehabilitation programs can provide relief, but more research is needed to establish their effectiveness. Preventive measures such as vaccination and the use of antiviral medications and metformin. It is imperative to conduct further research to develop evidence-based guidelines and gain a better understanding of the long-term implications of COVID-19. Long COVID could have substantial economic impact on the labor market, productivity, healthcare expenditures, and overall economic growth. To address the challenges patients with long-term complications face, there is a focus on strategies like promoting telework and flexible work arrangements to accommodate diverse symptoms, particularly chronic fatigue and other Long COVID effects. In conclusion, this review emphasizes the multifaceted complexity of Long COVID and the ongoing need to address its potential long-term health and economic impacts.

Notch ligands are biomarkers of anti-TNF response in RA patients.

Notch and its ligands play a critical role in rheumatoid arthritis (RA) pathogenesis. Hence, studies were conducted to delineate the functional significance of the Notch pathway in RA synovial tissue (ST) cells and the influence of RA therapies on their expression. Morphological studies reveal that JAG1, DLL4, and Notch1 are highly enriched in RA ST lining and sublining CD68+CD14+ MΦs. JAG1 and DLL4 transcription is jointly upregulated in RA MΦs reprogrammed by TLR4/5 ligation and TNF, whereas Syntenin-1 exposure expands JAG1, DLL4, and Notch1 expression levels in these cells. Single-cell RNA-seq data exhibit that JAG1 and Notch3 are overexpressed on all fibroblast-like synoviocyte (FLS) subpopulations, in parallel, JAG2, DLL1, and Notch1 expression levels are modest on RA FLS and are predominately potentiated by TLR4 ligation. Intriguingly, JAG1, DLL1/4, and Notch1/3 are presented on RA endothelial cells, and their expression is mutually reconfigured by TLR4/5 ligation in the endothelium. Synovial JAG1/JAG2/DLL1 or Notch1/3 transcriptomes were unchanged in patients who received disease-modifying anti-rheumatic drugs (DMARDs) or IL-6R Ab therapy regardless of disease activity score. Uniquely, RA MΦs and endothelial cells rewired by IL-6 displayed DLL4 transcriptional upregulation, and IL-6R antibody treatment disrupted RA ST DLL4 transcription in good responders compared to non-responders or moderate responders. Nevertheless, the JAG1/JAG2/DLL1/DLL4 transcriptome was diminished in anti-TNF good responders with myeloid pathotype and was unaltered in the fibroid pathotype except for DLL4. Taken together, our findings suggest that RA myeloid Notch ligands can serve as markers for anti-TNF responsiveness and trans-activate Notch receptors expressed on RA FLS and/or endothelial cells.

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.

Bullous Systemic Lupus Erythematosus Successfully Treated With Intravenous Immunoglobulin and Mycophenolate Mofetil.

Bullous systemic lupus erythematosus (BSLE) is a rare autoimmune blistering disorder of cutaneous lupus erythematosus (CLE) that typically manifests as an acute vesiculobullous eruption in a patient with systemic lupus erythematosus (SLE). Also, it can rarely present as the initial clinical manifestation of SLE. There is no established US Food and Drug Administration (FDA) therapy for BSLE. We report a case of a 71-year-old Hispanic woman with SLE and lupus nephritis classes III and V who presented to the hospital with a worsening rash with painful, ruptured blisters involving the upper arms, chest, and back. Our patient did not respond to topical or systemic steroids but improved rapidly to combination therapy with intravenous immunoglobulin (IVIg) and mycophenolate mofetil (MMF).

Vaccination in the Era of Immunosuppression.

Patients with autoimmune inflammatory rheumatic diseases (AIIRDs) are at increased risk for severe infections. Vaccine responses and safety profiles may differ between AIIRD patients and the general population. While patients with autoimmune inflammatory rheumatic diseases (AIIRDs) often experience diminished humoral responses and reduced vaccine efficacy, factors such as the type of immunosuppressant medications used and the specific vaccine employed contribute to these outcomes. Notably, individuals undergoing B cell depletion therapy tend to have poor vaccine immunogenicity. However, despite these considerations, vaccine responses are generally considered clinically sufficient. Ideally, immunosuppressed AIIRD patients should receive vaccinations at least two weeks before commencing immunosuppressive treatment. However, it is common for many patients to already be on immunosuppressants during the immunization process. Vaccination rarely triggers flares in AIIRDs; if flares occur, they are typically mild. Despite the heightened infection risk, including COVID-19, among AIIRD patients with rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, and other diseases on immunosuppressants, the vaccination rates remain suboptimal. The future directions of vaccination in the era of immunosuppression will likely involve customized vaccines with enhanced adjuvants and alternative delivery methods. By addressing the unique challenges faced by immunosuppressed individuals, we may improve vaccine efficacy, reduce the risk of infections, and ultimately enhance the health outcomes. Additionally, clinical trials to evaluate the safety and efficacy of temporarily discontinuing immunosuppressants during vaccination in various AIIRDs are crucial.

Corrigendum: Reproducibility and rigor in rheumatology research.

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

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.

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.

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.

Significance of IL-34 and SDC-1 in the pathogenesis of RA cells and preclinical models.

IL-34 shares a common receptor with M-CSF, while it can bind to other distinct receptors including protein-tyrosine phosphatase zeta (PTPζ), and syndecan1 (SDC-1). In physiological conditions, IL-34 has a critical role in the maintenance and development of Langerhans and microglial cells in part through PTPζ ligation. Conversely, in autoimmune diseases such as rheumatoid arthritis (RA), SDC-1-induced phosphorylation of M-CSFR was responsible for the pathological effect of IL-34 in patient cells and/or preclinical models. Intriguingly, enrichment of IL-34 is strongly linked to rheumatoid factor (RF), disease activity score (DAS)28, erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), and radiographic progression. In parallel, IL-34-induced naïve cell reprogramming into glycolytic RA CD14+CD86+GLUT1+ macrophage was dysregulated via M-CSFR or SDC-1 antibody therapy. Moreover, the inflammatory and erosive imprints of IL-34 arthritic mice were mitigated by glucose uptake inhibition and SDC-1, or RAG deficiency through nullifying macrophage metabolic rewiring and their ability to advance Th1/Th17 cell polarization. Consistently, IL-34-/- and SDC-1-/- mice could effectively impair CIA joint inflammation, osteoclast formation, and neovascularization by restraining monocyte infiltration as well as suppressing the inflammatory macrophage and T effector cell reconfiguration via metabolic deactivation. In conclusion, targeting IL-34/SDC-1 signaling, or its interconnected metabolites can uniquely intercept the crosstalk between glycolytic RA myeloid and lymphoid cells and their ability to trigger arthritis.

Immune-mediated lung diseases: A narrative review.

The role of immunity in the pathogenesis of various pulmonary diseases, particularly interstitial lung diseases (ILDs), is being increasingly appreciated as mechanistic discoveries advance our knowledge in the field. Immune-mediated lung diseases demonstrate clinical and immunological heterogeneity and can be etiologically categorized into connective tissue disease (CTD)-associated, exposure-related, idiopathic, and other miscellaneous lung diseases including sarcoidosis, and post-lung transplant ILD. The immunopathogenesis of many of these diseases remains poorly defined and possibly involves either immune dysregulation, abnormal healing, chronic inflammation, or a combination of these, often in a background of genetic susceptibility. The heterogeneity and complex immunopathogenesis of ILDs complicate management, and thus a collaborative treatment team should work toward an individualized approach to address the unique needs of each patient. Current management of immune-mediated lung diseases is challenging; the choice of therapy is etiology-driven and includes corticosteroids, immunomodulatory drugs such as methotrexate, cyclophosphamide and mycophenolate mofetil, rituximab, or other measures such as discontinuation or avoidance of the inciting agent in exposure-related ILDs. Antifibrotic therapy is approved for some of the ILDs (e.g., idiopathic pulmonary fibrosis) and is being investigated for many others and has shown promising preliminary results. A dire need for advances in the management of immune-mediated lung disease persists in the absence of standardized management guidelines.

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.

Potential limitations of activity tracking devices in monitoring effects of treatment for sarcoidosis.

INTRODUCTION:   activity tracker device usage can help analyze the impact of disease state and therapy on patients in clinical practice.  factors such as age, race, and gender may contribute to difficulties with using such technology.  Objective: we evaluated the effect of age, race, and gender on the usability of the Fitbit OneTM activity tracking device in sarcoidosis patients and the impact of device on sarcoidosis patients' activity. METHOD: patients participated in a six-month prospective study where were asked to wear a Fitbit OneTM activity tracker daily. device usage education was provided at study enrollment.  weekly data download and submission reports to participating centers was required. patients were asked to complete a post-study questionnaire reviewing the motivation of the activity tracker on daily activity. RESULTS: at three centers, 91 patients completed all study visits and the post study questionnaire with a mean age of 55 and 75% were female and 34% african american. accurate downloads occurred >75% of the time, regardless of age, race, or sex. results of the post-study questionnaire did not show a correlation between the likelihood of wearing the device and motivation to increase activity. CONCLUSION: using an activity tracking device to evaluate and/or correlated with quality of life (QOL) instruments may prove beneficial for gathering more data on patients.  age, race, and gender did not contribute to differences in usability among sarcoidosis patients.

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.

Syntenin-1-mediated arthritogenicity is advanced by reprogramming RA metabolic macrophages and Th1 cells.

OBJECTIVES: Syntenin-1, a novel endogenous ligand, was discovered to be enriched in rheumatoid arthritis (RA) specimens compared with osteoarthritis synovial fluid and normal synovial tissue (ST). However, the cellular origin, immunoregulation and molecular mechanism of syntenin-1 are undescribed in RA. METHODS: RA patient myeloid and lymphoid cells, as well as preclinical models, were used to investigate the impact of syntenin-1/syndecan-1 on the inflammatory and metabolic landscape. RESULTS: Syntenin-1 and syndecan-1 (SDC-1) co-localise on RA ST macrophages (MΦs) and endothelial cells. Intriguingly, blood syntenin-1 and ST SDC-1 transcriptome are linked to cyclic citrullinated peptide, erythrocyte sedimentation rate, ST thickness and bone erosion. Metabolic CD14+CD86+GLUT1+MΦs reprogrammed by syntenin-1 exhibit a wide range of proinflammatory interferon transcription factors, monokines and glycolytic factors, along with reduced oxidative intermediates that are downregulated by blockade of SDC-1, glucose uptake and/or mTOR signalling. Inversely, IL-5R and PDZ1 inhibition are ineffective on RA MΦs-reprogrammed by syntenin-1. In syntenin-1-induced arthritis, F4/80+iNOS+RAPTOR+MΦs represent glycolytic RA MΦs, by amplifying the inflammatory and glycolytic networks. Those networks are abrogated in SDC-1-/- animals, while joint prorepair monokines are unaffected and the oxidative metabolites are moderately replenished. In RA cells and/or preclinical model, syntenin-1-induced arthritogenicity is dependent on mTOR-activated MΦ remodelling and its ability to cross-regulate Th1 cells via IL-12 and IL-18 induction. Moreover, RA and joint myeloid cells exposed to Syntenin-1 are primed to transform into osteoclasts via SDC-1 ligation and RANK, CTSK and NFATc1 transcriptional upregulation. CONCLUSION: The syntenin-1/SDC-1 pathway plays a critical role in the inflammatory and metabolic landscape of RA through glycolytic MΦ and Th1 cell cross-regulation (graphical abstract).

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.

Examination of eQTL Polymorphisms Associated with Increased Risk of Progressive Complicated Sarcoidosis in European and African Descent Subjects.

Background: A limited pool of SNPs are linked to the development and severity of sarcoidosis, a systemic granulomatous inflammatory disease. By integrating genome-wide association studies (GWAS) data and expression quantitative trait loci (eQTL) single nuclear polymorphisms (SNPs), we aimed to identify novel sarcoidosis SNPs potentially influencing the development of complicated sarcoidosis. Methods: A GWAS (Affymetrix 6.0) involving 209 African-American (AA) and 193 European-American (EA, 75 and 51 complicated cases respectively) and publicly-available GWAS controls (GAIN) was utilized. Annotation of multi-tissue eQTL SNPs present on the GWAS created a pool of ~46,000 eQTL SNPs examined for association with sarcoidosis risk and severity (Logistic Model, Plink). The most significant EA/AA eQTL SNPs were genotyped in a sarcoidosis validation cohort (n=1034) and cross-validated in two independent GWAS cohorts. Results: No single GWAS SNP achieved significance (p<1x10-8), however, analysis of the eQTL/GWAS SNP pool yielded 621 eQTL SNPs (p<10-4) associated with 730 genes that highlighted innate immunity, MHC Class II, and allograft rejection pathways with multiple SNPs validated in an independent sarcoidosis cohort (105 SNPs analyzed) (NOTCH4, IL27RA, BTNL2, ANXA11, HLA-DRB1). These studies confirm significant association of eQTL/GWAS SNPs in EAs and AAs with sarcoidosis risk and severity (complicated sarcoidosis) involving HLA region and innate immunity. Conclusion: Despite the challenge of deciphering the genetic basis for sarcoidosis risk/severity, these results suggest that integrated eQTL/GWAS approaches may identify novel variants/genes and support the contribution of dysregulated innate immune responses to sarcoidosis severity.

Adalimumab in the treatment of cardiac sarcoidosis: Single center case series and narrative literature review.

Background: Tumor necrosis factor (TNF) inhibitors have been used in the treatment of cardiac sarcoidosis, infliximab being the most commonly used. We have previously reported a case of effective treatment of cardiac sarcoidosis using adalimumab. Objective: To describe our experience of using adalimumab in the treatment of cardiac sarcoidosis. Methods: We conducted a retrospective study to evaluate patients with cardiac sarcoidosis who received adalimumab treatment at the University of Illinois Health between 2011 and 2022. The outcome was evaluated by assessing safety, tolerability, and ability to taper systemic corticosteroids therapy following initiation of adalimumab. Results: Seven patients met the inclusion criteria. Clinical responses to adalimumab were universally positive. Corticosteroid therapy was discontinued in five patients and the dose was reduced in two patients. Furthermore, adalimumab was well tolerated, and no adverse events were reported. Conclusion: Adalimumab was safe and well-tolerated in seven patients with cardiac sarcoidosis seen at our medical center and exhibited corticosteroid-sparing effects. Our observation further warrants large prospective studies to evaluate the safety and efficacy of adalimumab in the treatment of cardiac sarcoidosis.

Atypical ulcers: a stepwise approach for clinicians.

Chronic ulcers are associated with significant morbidity and mortality. Typical ulcers are due to venous insufficiency, diabetes, ischemia, pressure, and lymphedema. A chronic ulcer that does not respond to standard therapies should be reevaluated for potential atypical etiologies. Atypical ulcers are less common and more difficult to diagnose due to a wide range of possible etiologies, including inflammatory (autoimmune), neoplastic, vasculopathy, hematologic, infectious, drug-induced, or external. No standardized approach to the management of complex atypical ulcers exists. In this review, a stepwise approach to atypical ulcers is proposed with the aim of assisting physicians in their identification and diagnosis. If perfusion is adequate and there are no signs of infection, then the authors recommend obtaining an ulcer biopsy for microbiologic, DIF, and histopathologic evaluation as the criterion standard for diagnosis. Laboratory testing, including an autoimmune panel, a hypercoagulable panel, and an infectious diseases panel, can further aid in diagnosis. Atypical ulcers often require multidisciplinary care, with input from specialists in rheumatology, dermatology, infectious diseases, wound care, vascular surgery, hematology, and oncology. Effective communication within the health care team is essential for accurate diagnosis and management of atypical ulcers. Active dialogue between providers can improve consult efficiency and ultimately lower the cost of care.