-
Seminars in Respiratory and Critical... Jun 2024Systemic Lupus Erythematosus (SLE) is a multifaceted, multisystem autoimmune disorder with diverse clinical expressions. While prevalence reports vary widely, pulmonary... (Review)
Review
Systemic Lupus Erythematosus (SLE) is a multifaceted, multisystem autoimmune disorder with diverse clinical expressions. While prevalence reports vary widely, pulmonary involvement accounts for significant morbidity and mortality in SLE. This comprehensive review explores the spectrum of pulmonary disease in SLE, including upper airway manifestations (e.g., laryngeal affection), lower airway conditions (e.g., bronchitis, bronchiolitis, bronchiectasis), parenchymal diseases (e.g., interstitial lung disease, acute lupus pneumonitis, diffuse alveolar hemorrhage), pleural diseases (e.g., serositis, shrinking lung syndrome), and vascular diseases (e.g., pulmonary arterial hypertension, pulmonary embolism, acute reversible hypoxemia syndrome). We discuss diagnostic modalities, treatment strategies, and prognosis for each pulmonary manifestation. With diagnostics remaining a challenge and with the absence of standardized treatment guidelines, we emphasize the need for evidence-based guidelines to optimize patient care and improve outcomes in this complex disease.
Topics: Humans; Lupus Erythematosus, Systemic; Lung Diseases; Prognosis
PubMed: 38547915
DOI: 10.1055/s-0044-1782653 -
Indian Journal of Pediatrics Sep 2023Systemic lupus erythematosus (SLE) is a systemic autoimmune disease, that mainly affects skin, joints and kidneys but can affect any organ in the body. It is... (Review)
Review
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease, that mainly affects skin, joints and kidneys but can affect any organ in the body. It is characterized by presence of multiple autoantibodies like ANA, antibodies to dsDNA and RNA associated proteins. The major mechanism leading to tissue damage includes immune complex mediated complement activation, interferon alpha release by plasmacytoid dendritic cells, NETosis by neutrophils as well as defects in monocytes leading to poor clearance of cellular debris and direct cellular dysfunction mediated by antibodies. A child can present with pyrexia of unknown origin, immune mediated cytopenias, malar rash, oral ulcers, serositis, glomerulonephritis or nervous system dysfunction. As renal disease has a bearing on the long term impact, all children should have urine exam and blood pressure measurement done to rule out renal disease. The treatment varies depending on the severity and organs involved. In life or organ threatening situations, pulse methylprednisolone is used. Hydroxychloroquine, Mycophenolate mofetil, Azathioprine and Cyclophosphamide are the commonly used drugs in SLE. Over the years the prognosis of SLE has improved probably due to early diagnosis and better use of immunosuppressive treatment, regular follow up and treatment of co-morbidities. The 10-year survival now approaches 90% and with advent of new and targeted therapy it is hoped that the morbidity and organ damage can also be minimized.
PubMed: 37713101
DOI: 10.1007/s12098-023-04833-0 -
Lupus Aug 2023Systemic lupus erythematosus (SLE) is non-organ specific autoimmune disease with mainly skin, joint, and kidney involvement. SLE-related acute lung disease (ALD) is...
INTRODUCTION
Systemic lupus erythematosus (SLE) is non-organ specific autoimmune disease with mainly skin, joint, and kidney involvement. SLE-related acute lung disease (ALD) is rare, poorly investigated and can lead to acute respiratory failure. We conducted a retrospective study aiming to describe clinical features, treatments and outcome of SLE-related APD.
METHODS
We retrospectively included all patients with SLE and ALD admitted from November 1996 and September 2018 to La Pitié-Salpêtrière Hospital, after exclusion of viral or bacterial lung infection, cardiac failure or any other alternate diagnosis.
RESULTS
During the time of the study, 14 patients with 16 episodes were admitted to our center: female 79%, mean age ± SD at admission 24 ± 11 years. ALD was inaugural of the SLE in 70% cases. SLE main organ involvement were: arthritis 93%, skin 79%, serositis 79%, hematological 79%, kidney 64%, neuropsychiatric 36% and cardiac 21%. 11 episodes required ICU admission for a median time of 8 days. Chest CT-scan revealed mostly basal consolidation and ground-glass opacities. When available, bronchoalveolar lavage mostly revealed a neutrophilic alveolitis with alveolar hemorrhage in 67% cases. Symptomatic respiratory treatments were: oxygen 81%, high-flow nasal canula oxygen 27%, non-invasive ventilation 36%, mechanical ventilation 64% and venovenous extracorporeal membrane oxygenation 18%. SLE-specific treatments were: corticosteroids 100%, cyclophosphamide 56% and plasma exchange 25%. All patients but one survived to ICU and hospital discharge. Two patients had a relapse of SLE-related ALD but none had interstitial lung disease during follow-up.
CONCLUSION
Systemic lupus erythematosus-related acute respiratory failure is a severe event, mostly occurring at SLE onset, typical harboring a basal consolidation pattern on chest CT-scan and alveolar hemorrhage on BAL pathological examination. Mortality in our cohort is lower than previously reported but these results needs to be confirmed in further larger studies.
Topics: Humans; Female; Lupus Erythematosus, Systemic; Retrospective Studies; Lung Diseases; Hemorrhage; Respiratory Distress Syndrome; Lung; Respiratory Insufficiency
PubMed: 37395001
DOI: 10.1177/09612033231188034 -
Journal of Leukocyte Biology Oct 2023Systemic juvenile idiopathic arthritis is a chronic pediatric inflammatory disease of unknown etiology, characterized by fever, rash, hepatosplenomegaly, serositis, and...
Systemic juvenile idiopathic arthritis is a chronic pediatric inflammatory disease of unknown etiology, characterized by fever, rash, hepatosplenomegaly, serositis, and arthritis. We hypothesized that intercellular communication, mediated by extracellular vesicles, contributes to systemic juvenile idiopathic arthritis pathogenesis and that the number and cellular sources of extracellular vesicles would differ between inactive and active states of systemic juvenile idiopathic arthritis and healthy controls. We evaluated plasma from healthy pediatric controls and patients with systemic juvenile idiopathic arthritis with active systemic flare or inactive disease. We isolated extracellular vesicles by size exclusion chromatography and determined total extracellular vesicle abundance and size distribution using microfluidic resistive pulse sensing. Cell-specific extracellular vesicle subpopulations were measured by nanoscale flow cytometry. Isolated extracellular vesicles were validated using a variety of ways, including nanotracking and cryo-electron microscopy. Extracellular vesicle protein content was analyzed in pooled samples using mass spectrometry. Total extracellular vesicle concentration did not significantly differ between controls and patients with systemic juvenile idiopathic arthritis. Extracellular vesicles with diameters <200 nm were the most abundant, including the majority of cell-specific extracellular vesicle subpopulations. Patients with systemic juvenile idiopathic arthritis had significantly higher levels of extracellular vesicles from activated platelets, intermediate monocytes, and chronically activated endothelial cells, with the latter significantly more elevated in active systemic juvenile idiopathic arthritis relative to inactive disease and controls. Protein analysis of isolated extracellular vesicles from active patients showed a proinflammatory profile, uniquely expressing heat shock protein 47, a stress-inducible protein. Our findings indicate that multiple cell types contribute to altered extracellular vesicle profiles in systemic juvenile idiopathic arthritis. The extracellular vesicle differences between systemic juvenile idiopathic arthritis disease states and healthy controls implicate extracellular vesicle-mediated cellular crosstalk as a potential driver of systemic juvenile idiopathic arthritis disease activity.
Topics: Humans; Child; Arthritis, Juvenile; Cryoelectron Microscopy; Endothelial Cells; Monocytes; Extracellular Vesicles
PubMed: 37201912
DOI: 10.1093/jleuko/qiad059 -
Clinical Rheumatology Aug 2023Endothelial dysfunction (ED) has an important role in the pathogenesis of systemic lupus erythematosus (SLE). Studies on other inflammatory diseases show that salusin-β...
OBJECTIVE
Endothelial dysfunction (ED) has an important role in the pathogenesis of systemic lupus erythematosus (SLE). Studies on other inflammatory diseases show that salusin-β with various mechanisms may play a role in the promotion of ED and inflammation. The aim of this study was to measure serum salusin-β levels in SLE patients and evaluate it as a potential biomarker in assessing SLE activity and predicting organ involvement.
METHODS
In a cross-sectional study, 60 patients diagnosed with SLE and 30 age- and sex-matched healthy controls were enrolled. Disease activity of SLE patients was assessed by the systemic lupus erythematosus disease activity index 2000 (SLEDAI-2 K). Serum levels of salusin-ß were measured using a human salusin-ß enzyme-linked immunosorbent assay kit.
RESULTS
Serum salusin-β levels in SLE and control groups were 474.2 ± 117.1 pg/ml and 157.7 ± 88.7 pg/ml, respectively. The difference was significant (P = 0.001). There was no significant correlation between serum salusin-β levels with age (r = - 0.06, P = 0.632) and SLEDAI (r = - 0.185, P = 0.158). In patients with nephritis and thrombosis, serum salusin-β was significantly higher. In addition, in patients with serositis, serum salusin-β was significantly lower. Multiple linear regression analysis showed that serum salusin-β levels retained a significant association with nephritis and thrombosis after model adjustment for serositis, nephritis, and thrombosis.
CONCLUSIONS
Our findings showed that salusin-β might have a possible role in the pathogenesis of SLE. Salusin-β may be a potential biomarker for nephritis and thrombosis in SLE. Key Points • Serum salusin-β levels were significantly higher in SLE patients than the control group. • There was no significant correlation between serum salusin-β levels with age and SLEDAI. • Serum salusin-β levels retained a significant association with nephritis and thrombosis.
Topics: Humans; Serositis; Cross-Sectional Studies; Lupus Erythematosus, Systemic; Nephritis; Biomarkers; Vascular Diseases; Lupus Nephritis
PubMed: 37120490
DOI: 10.1007/s10067-023-06610-y -
Advances in Rheumatology (London,... Aug 2023The p53 and p21 proteins are important regulators of cell cycle and apoptosis and may contribute to autoimmune diseases, such as systemic lupus erythematosus (SLE). As...
BACKGROUND
The p53 and p21 proteins are important regulators of cell cycle and apoptosis and may contribute to autoimmune diseases, such as systemic lupus erythematosus (SLE). As genetic polymorphisms may cause changes in protein levels and functions, we investigated associations of TP53 and p21 (CDKN1A) polymorphisms (p53 72 G > C-rs1042522; p53 PIN3-rs17878362; p21 31 C > A-rs1801270; p21 70 C > T-rs1059234) with the development of systemic lupus erythematosus (SLE) in a Southeastern Brazilian population.
METHODS
Genotyping of 353 female volunteers (cases, n = 145; controls, n = 208) was performed by polymerase chain reaction, restriction fragment length polymorphism and/or DNA sequencing. Associations between TP53 and p21 polymorphisms and SLE susceptibility and clinical manifestations of SLE patients were assessed by logistic regression analysis.
RESULTS
Protective effect was observed for the genotype combinations p53 PIN3 A1/A1-p21 31 C/A, in the total study population (OR 0.45), and p53 PIN3 A1/A2-p21 31 C/C, in non-white women (OR 0.28). In Whites, p53 72 C-containing (OR 3.06) and p53 PIN3 A2-containing (OR 6.93) genotypes were associated with SLE risk, and higher OR value was observed for the combined genotype p53 72 G/C-p53 PIN3 A1/A2 (OR 9.00). Further, p53 PIN3 A1/A2 genotype was associated with serositis (OR 2.82), while p53 PIN3 A2/A2 and p53 72 C/C genotypes were associated with neurological disorders (OR 4.69 and OR 3.34, respectively).
CONCLUSIONS
Our findings showed that the TP53 and p21 polymorphisms included in this study may have potential to emerge as SLE susceptibility markers for specific groups of patients. Significant interactions of the TP53 polymorphisms with serositis and neurological disorders were also observed in SLE patients.
Topics: Female; Humans; Cyclin-Dependent Kinase Inhibitor p21; Lupus Erythematosus, Systemic; Polymorphism, Genetic; Serositis; Tumor Suppressor Protein p53
PubMed: 37605254
DOI: 10.1186/s42358-023-00320-4 -
The Journal of the Association of... Mar 2024has a higher prevalence in India than in the world. Legionaries' disease most commonly involves the lungs but because of increased awareness, extrapulmonary...
BACKGROUND
has a higher prevalence in India than in the world. Legionaries' disease most commonly involves the lungs but because of increased awareness, extrapulmonary manifestations are also being diagnosed more frequently.
CASE DESCRIPTION
We present a case of a young female with acute onset of fever and chest pain. On initial investigation, an electrocardiogram (ECG) reported widespread pulse rate (PR) depression suggestive of pericarditis which was confirmed by ECG. High-resolution computed tomography (HRCT) thorax suggested mild bilateral pleural effusion with normal lung parenchyma. elevated erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) added to the diagnosis of serositis. Serological study for atypical organisms was remarkable for positive immunoglobulin M (IgM) for . She was treated with a high dose of steroids and azithromycin successfully.
CONCLUSION
Isolated extrapulmonary presentation of legionaries disease is often overlooked and is common. So it should be always included in the diagnostic armamentarium as treatment is highly efficacious if started early.
Topics: Humans; Female; Serositis; Azithromycin; Adult; Anti-Bacterial Agents; Legionellosis; Legionella; Electrocardiography; Tomography, X-Ray Computed; Legionnaires' Disease
PubMed: 38736126
DOI: 10.59556/japi.72.0361 -
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 -
Lupus Oct 2023To determine the risk factors of pulmonary arterial hypertension (PAH) related to systemic lupus erythematosus (SLE) through systematic reviews and meta-analyses. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine the risk factors of pulmonary arterial hypertension (PAH) related to systemic lupus erythematosus (SLE) through systematic reviews and meta-analyses.
METHODS
We undertook electronic search strategies using Medline via PubMed, Embase, Web of Science, and Cochrane Library up to April 11, 2023. Study selection and data extraction were performed by 2 authors independently. We made risk of bias judgments based on the Newcastle-Ottawa Scale (NOS). Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated to estimate the overall effect sizes of potential risk factors for PAH in SLE patients. Univariate and multivariate meta-regression models were used to assess the independent effects of each risk factor on PAH. Sensitivity analyses were also conducted to explore potential sources of heterogeneity.
RESULTS
A total of 19 articles were included in this meta-analysis, and the results showed that gender (female) [RR = 1.04, 95% CI (1.02, 1.06), = .0001], interstitial lung disease [RR = 4.36, 95% CI (2.42, 7.85), = .0001], alopecia [RR = 1.39, 95% CI (1.06, 1.83), = .017], Raynaud's phenomenon [RR = 1.83, 95% CI (1.41, 2.37), = .0001], systemic hypertension [RR = 1.30, 95% CI (1.07, 1.58), = .007], serositis [RR = 2.29, 95% CI (1.89, 2.77), = .0001], pericardial effusion [RR = 3.33, 95% CI (2.20, 5.05), = .0001], anti-RNP [RR = 1.86, 95% CI (1.19, 2.91), = .006], anti-SSA [RR = 1.28, 95% CI (1.01, 1.62), = .041], anti-SSB [RR = 1.38, 95% CI (1.19, 1.60), = .0001], anti-U1RNP [RR = 1.58, 95% CI (1.07, 2.34), = .023], thrombocytopenia [RR = 1.38, 95% CI (1.14, 1.68), = .001], and current smokers [RR = 2.20, 95% CI (1.19, 4.06), = .012] were all risk factors for PAH related to SLE.
CONCLUSION
PAH is a serious complication of SLE. Since prognosis of SLE patients after the occurrence of PAH is poor, routine examination should be conducted for SLE patients with PAH risk factors.
Topics: Humans; Female; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Lupus Erythematosus, Systemic; Risk Factors; Prognosis
PubMed: 37699157
DOI: 10.1177/09612033231202398