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Frontiers in Pharmacology 2022Systemic lupus erythematosus (SLE) is a complex autoimmune disease with systemic clinical manifestations including, but not limited to, rash, inflammatory arthritis,... (Review)
Review
Systemic lupus erythematosus (SLE) is a complex autoimmune disease with systemic clinical manifestations including, but not limited to, rash, inflammatory arthritis, serositis, glomerulonephritis, and cerebritis. Treatment options for SLE are expanding and the increase in our understanding of the immune pathogenesis is leading to the development of new therapeutics. Autoantibody formation and immune complex formation are important mediators in lupus pathogenesis, but an important role of the type I interferon (IFN) pathway has been identified in SLE patients and mouse models of lupus. These studies have led to the development of therapeutics targeting type I IFN and related pathways for the treatment of certain manifestations of SLE. In the current narrative review, we will discuss the role of type I IFN in SLE pathogenesis and the potential translation of these data into strategies using type I IFN as a biomarker and therapeutic target for patients with SLE.
PubMed: 36726783
DOI: 10.3389/fphar.2022.1046687 -
Cureus Oct 2021Background Dengue fever, more prevalent in Asia, is a highly neglected vector-borne disease. It has a varied presentation ranging from common fever to atypical...
Background Dengue fever, more prevalent in Asia, is a highly neglected vector-borne disease. It has a varied presentation ranging from common fever to atypical presentation as encephalitis. This study aimed to analyze the demographic and clinical profile of dengue patients admitted to a tertiary care center in Tamilnadu. Methodology This retrospective study was performed by collecting patient data from the medical records department for the years 2012 to 2014. A total of 150 patients with 50 patients from each year were selected. The patient's demographic data, clinical profile, management, and outcome were noted. Patients were divided into three groups as per the World Health Organization's 2009 classification. Results Most dengue cases occurred from October to December (70.7%). The number of male and female patients was almost equal (77 [51.3%] and 73 [48.7%], respectively). The middle-aged group (21-40 years) was commonly affected (54%). The mean age was 29 ± 13.20 years. Fever was the most common symptom (100%), followed by lethargy (81.3%) and myalgia (60.7%). Overall, 10% of patients had comorbidities such as diabetes, hypertension, and ischemic heart disease. Moreover, 22.7% of patients had dengue with warning signs, and severe dengue was seen in 19.3% of patients. A significant difference was noted in the total count, comorbidities, serositis, and the duration of hospitalization between the groups. No mortality was recorded in the study population. Conclusions Dengue is very common in the middle-aged group. Patients with severe dengue had significant leucopenia, several comorbidities, and serositis. The mortality can be reduced to <1% and even zero in severe dengue according to our study with close monitoring and supportive care.
PubMed: 34692260
DOI: 10.7759/cureus.18500 -
Pediatric Surgery International Aug 2022Acute appendicitis is the most common surgical emergency in children. Diagnosis and management are often straightforward. However, familial Mediterranean fever is an... (Review)
Review
Acute appendicitis is the most common surgical emergency in children. Diagnosis and management are often straightforward. However, familial Mediterranean fever is an important condition to consider in the assessment of children with acute abdominal pain, particularly in children with an origin in eastern Mediterranean basin where the disease is common. The key feature of familial Mediterranean fever is relapsing episodes of fever and serositis including peritonitis, pleurisy, or arthritis. The disease is treated with colchicine that prevents acute attacks, control subclinical inflammation between the attacks and the long-term complication of amyloidosis. The acute attacks may be a challenge to identify and distinguish from other causes of acute abdomen, including acute appendicitis, but also small bowel obstruction. Ultrasound and CT scan findings are nonspecific during acute attacks of familial Mediterranean fever, but imaging is useful to identify acute appendicitis and small bowel obstruction. The purpose of this article was to increase the awareness and knowledge of familial Mediterranean fever and provide support for the paediatric surgeon in the clinical care of these children in parts of the world where familial Mediterranean fever is rare.
Topics: Abdominal Pain; Acute Disease; Appendicitis; Child; Colchicine; Familial Mediterranean Fever; Fever; Humans; Intestinal Obstruction
PubMed: 35737103
DOI: 10.1007/s00383-022-05153-8 -
Clinical and Experimental Rheumatology Sep 2022Familial Mediterranean fever (FMF) is a hereditary auto-inflammatory disease, characterised by recurrent episodes of fever and serositis. Since 1972, colchicine is the... (Review)
Review
Familial Mediterranean fever (FMF) is a hereditary auto-inflammatory disease, characterised by recurrent episodes of fever and serositis. Since 1972, colchicine is the drug of choice for FMF. It is effective in preventing the attacks and withholding amyloidosis in most patients with FMF. Colchicine blood and tissue levels are regulated by a glycoprotein pump (GLP) and by Cytochrome P450 3A4 (CYP450 3A4). It is secreted through the bile system and the kidneys. Over the years several problems have been raised following the use of colchicine in FMF. These include potential side effects (particularly gastrointestinal), non-compliance, inefficacy due to drug resistance, many drug-drug interactions and high risk for intoxication due to a narrow therapeutic range. In addition, colchicine does not prevent protracted febrile myalgia or exertional leg pain. Based upon our current understanding of the pathogenesis of FMF, it seems that anti-interleukin-1 (anti-IL-1) agents can solve many of the aforementioned problems related to colchicine therapy. The gastrointestinal side effects of colchicine are extremely uncommon with anti-IL-1 biologics. Drug-drug interactions are also unlikely, and their therapeutic window is not narrow. The once daily injection of anakinra, the once weekly injection of rilonacept, and the once monthly injection of canakinumab result in a better compliance to therapy. Nevertheless, there are no controlled trials showing the efficacy of anti-IL-1 agents in preventing amyloidosis or their safety in pregnancy. Therefore, it is still needed to give IL-1 blockers with concomitant colchicine in its tolerable dose effective in preventing amyloidosis (1.5 mg daily in adult).
Topics: Adult; Amyloidosis; Colchicine; Familial Mediterranean Fever; Female; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Motivation; Pregnancy
PubMed: 36062765
DOI: 10.55563/clinexprheumatol/obb2ds -
BMJ Case Reports Jan 2021We report a case of a 42-year-old man who presented with acute epigastric and retrosternal chest pain and exertional dyspnoea, and was subsequently diagnosed with...
We report a case of a 42-year-old man who presented with acute epigastric and retrosternal chest pain and exertional dyspnoea, and was subsequently diagnosed with polyserositis secondary to post- infection. A CT scan showed a large pericardial effusion requiring pericardiocentesis, small bilateral pleural effusions and small amount of ascites. Several serological tests were done, which were all found to be normal. Pericardial and pleural fluid aspirates revealed an exudate. Culture of the pleural fluid yielded growth of and this was deemed the cause of the polyserositis, which is rare. The patient made a spontaneous recovery. He was started on colchicine by the cardiologists to help prevent pericardial fluid recurrence and this was continued for 3 months. A dental review confirmed the presence of dental caries, the possible source of infection. On follow-up, the patient remained well with no further relapses.
Topics: Adult; Anti-Inflammatory Agents; Ascites; Colchicine; Humans; Male; Pericardial Effusion; Pericardiocentesis; Pleural Effusion; Serositis; Streptococcal Infections; Streptococcus mitis; Tomography, X-Ray Computed
PubMed: 33472801
DOI: 10.1136/bcr-2020-236704 -
Lupus Science & Medicine Apr 2023SLE is an autoimmune disease that predominantly affects women. As most epidemiological and interventional studies are on populations with a clear female prevalence, the...
BACKGROUND
SLE is an autoimmune disease that predominantly affects women. As most epidemiological and interventional studies are on populations with a clear female prevalence, the influence of gender in disease course, drug response and damage accrual is yet to be fully explored and comprehended.
OBJECTIVES
To describe gender differences in disease course, comorbidities, use of medications and long-term outcomes of a large cohort of patients with SLE.
METHODS
Retrospective gender-based analysis of prospectively collected data from a monocentric cohort of Caucasian patients with SLE with at least 1 year of follow-up.
RESULTS
417 patients were included, 51 men and 366 women. Men displayed a significantly higher median age at disease onset and diagnosis and a higher prevalence of late-onset SLE, serositis at disease onset, antiphospholipid syndrome (APS) and use of mycophenolate within the first year of disease. Women had a higher prevalence of haematological abnormalities, a higher cumulative exposure to azathioprine and higher cumulative dose of glucocorticoids at 5 years. Male patients had a shorter time to first damage item and a higher prevalence of damage at 1 and 5 years, but this association was no longer significant when late-onset patients were excluded. No differences were found in prevalence of childhood onset, delay between onset and diagnosis, time to renal involvement and histology, cumulative autoantibody positivity, number of flares and hospitalisations, median SLE Damage Index score, type of damage, age and time to first cardiovascular event, chronic kidney disease and death.
CONCLUSIONS
In our cohort, clinical manifestations and disease course were similar in male and female patients; however, male patients displayed higher prevalence of APS and early damage accrual probably due to the later disease onset. These data highlight the importance of an intensive follow-up, prevention and treatment of complications in this category of patients, especially in the first years of disease.
Topics: Humans; Male; Female; Retrospective Studies; Sex Factors; Lupus Erythematosus, Systemic; Antiphospholipid Syndrome; Glucocorticoids; Disease Progression
PubMed: 37185240
DOI: 10.1136/lupus-2022-000880 -
Cureus Sep 2022Rhupus syndrome, a rare coexistence of systemic lupus erythematosus (SLE) and rheumatoid arthritis, is characterized by symmetrical erosive polyarthritis and permanent...
Rhupus syndrome, a rare coexistence of systemic lupus erythematosus (SLE) and rheumatoid arthritis, is characterized by symmetrical erosive polyarthritis and permanent deformities in addition to the clinical and serological characteristics of SLE. Its prognosis is further complicated by neurological and hematological involvement, which dramatically lowers patients' perceptions of their quality of life in terms of their health. Rhupus individuals have significantly less kidney involvement than SLE patients do. We present a case of a young female who had symmetric, bilateral, erosive polyarthritis for one and a half years preceding the signs and symptoms of SLE, which occurred about six months later.
PubMed: 36249648
DOI: 10.7759/cureus.29018 -
Autoimmunity Reviews Nov 2022Undifferentiated connective tissue disease (UCTD) encapsulates a broad range of conditions including incomplete forms of systemic lupus erythematosus (SLE) and systemic... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Undifferentiated connective tissue disease (UCTD) encapsulates a broad range of conditions including incomplete forms of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc), some of whom progress to a formal clinical diagnosis over time. This systematic review (SR) and meta-analysis aimed to identify clinical and laboratory features and biomarkers that can predict progression of UCTD.
METHODS
A systematic literature search was carried out on MEDLINE, EMBASE and the Cochrane Central Register of Randomized Controlled Trials. Abstracts and full-text manuscripts were screened by two reviewers. Publications were included if they included at least 20 UCTD patients, a minimum of six months of follow up, and provided data on at least one risk factor for developing a defined CTD. The QUIPS tool was used to assess risk of bias (RoB) and GRADE for grading the quality of the evidence. The study is registered with PROSPERO (ID: CRD42021237725).
RESULTS
Fifty-nine studies were included in the SR, and forty-one in the meta-analysis. The predictors for progression to SLE with the highest certainty of evidence included those with younger age (MD -5.96 [-11.05-0.87 years]), serositis (RR 2.69 [1.61-4.51]), or the presence of anti-dsDNA antibodies (RR 4.27 [1.92-9.51]). For SSc, the highest certainty of evidence included puffy fingers (RR [3.09 [1.48-6.43]), abnormal nailfold changes (NFC) (avascular areas [RR 5.71 (3.03-10.8)] or active or late SSc pattern [RR 2.24 (1.25-4.01)] and anti-topoisomerase-I (RR 1.83 [1.45-2.30]). No novel biomarkers were included in the meta-analysis; however HLA molecules, regulatory T cell shift, pro-inflammatory cytokines and complement activation products were identified as potential predictors for evolution of disease.
CONCLUSIONS
Clinical and immunological parameters may predict which patients with UCTD progress to definitive disease; however, the heterogeneous nature and RoB in most studies limits the ability to apply these results in routine clinical practice. Limited data suggest that some novel biomarkers may provide additional predictive value but these will need larger well designed studies to fully delineate their clinical utility.
Topics: Humans; Undifferentiated Connective Tissue Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Scleroderma, Systemic; Biomarkers; Disease Progression
PubMed: 36031048
DOI: 10.1016/j.autrev.2022.103184 -
Microbiology Spectrum Oct 2022Duck infectious serositis, also known as Riemerella anatipestifer disease, infects domestic ducks, geese, and turkeys and wild birds. However, the regulatory mechanism...
Duck infectious serositis, also known as Riemerella anatipestifer disease, infects domestic ducks, geese, and turkeys and wild birds. However, the regulatory mechanism of its pathogenicity remains unclear. The PhoPR two-component system (TCS) was first reported in Gram-negative bacteria in our previous research and was demonstrated to be involved in virulence and gene expression. Here, DNA affinity purification sequencing (DAP-seq) was applied to further explore the regulation of PhoPR in relation to pathogenicity in R. anatipestifer. A conserved motif was identified upstream of 583 candidate target genes which were directly regulated by PhoP. To further confirm the genes which are regulated by PhoR and PhoP, single-gene-deletion strains were constructed. The results of transcriptome analysis using next-generation RNA sequencing showed 136 differentially expressed genes (DEGs) between the Δ strain and the wild type (WT) and 183 DEGs between the Δ strain and the WT. The candidate target genes of PhoP were further identified by combining transcriptome analysis and DAP-seq, which revealed that the main direct regulons of PhoP are located on the membrane and PhoP is involved in regulating aerotolerance. Using the duck model, the pathogenicity of Δ and Δ mutants was found to be significantly lower than that of the WT. Together, our findings provide insight into the direct regulation of PhoP and suggest that is essential for the pathogenicity of R. anatipestifer. The gene deletion strains are expected to be candidate live vaccine strains of R. anatipestifer which can be used as ideal genetic engineering vector strains for the expression of foreign antigens. Riemerella anatipestifer is a significant pathogen with high mortality in the poultry industry that causes acute septicemia and infectious polyserositis in ducks, chickens, geese, and other avian species. Previously, we characterized the two-component system encoded by and found that R. anatipestifer almost completely lost its pathogenicity for ducklings when was deleted. However, the mechanism of PhoPR regulation of virulence in R. anatipestifer had not been deeply explored. In this study, we utilized DAP-seq to explore the DNA-binding sites of PhoP as a response regulator in the global genome. Furthermore, and were deleted separately, and transcriptomics analysis of the corresponding gene deletion strains was performed. We identified a series of directly regulated genes of the PhoPR two-component system. The duckling model showed that both PhoP and PhoR are essential virulence-related factors in R. anatipestifer.
Topics: Animals; Bacterial Proteins; Chickens; Ducks; Flavobacteriaceae Infections; Poultry Diseases; Vaccines, Attenuated; Virulence; Virulence Factors; Genome, Bacterial
PubMed: 36197298
DOI: 10.1128/spectrum.01883-22 -
Cell Reports. Medicine May 2024Systemic lupus erythematosus (SLE) displays a hallmark interferon (IFN) signature. Yet, clinical trials targeting type I IFN (IFN-I) have shown variable efficacy, and...
Systemic lupus erythematosus (SLE) displays a hallmark interferon (IFN) signature. Yet, clinical trials targeting type I IFN (IFN-I) have shown variable efficacy, and blocking IFN-II failed to treat SLE. Here, we show that IFN type levels in SLE vary significantly across clinical and transcriptional endotypes. Whereas skin involvement correlated with IFN-I alone, systemic features like nephritis associated with co-elevation of IFN-I, IFN-II, and IFN-III, indicating additive IFN effects in severe SLE. Notably, while high IFN-II/-III levels without IFN-I had a limited effect on disease activity, IFN-II was linked to IFN-I-independent transcriptional profiles (e.g., OXPHOS and CD8GZMH cells), and IFN-III enhanced IFN-induced gene expression when co-elevated with IFN-I. Moreover, dysregulated IFNs do not explain the IFN signature in 64% of patients or clinical manifestations including cytopenia, serositis, and anti-phospholipid syndrome, implying IFN-independent endotypes in SLE. This study sheds light on mechanisms underlying SLE heterogeneity and the variable response to IFN-targeted therapies in clinical trials.
Topics: Humans; Lupus Erythematosus, Systemic; Interferons; Female; Adult; Male; Transcriptome; Interferon Type I; Middle Aged; Transcription, Genetic; Gene Expression Regulation
PubMed: 38744279
DOI: 10.1016/j.xcrm.2024.101569