Symptoms Of Systemic Lupus Erythematosus Research Articles

Effects of Nigella sativa on disease activity, T lymphocytes and inflammatory cytokine profiles in pediatric systemic lupus erythematosus: A randomized controlled trial

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with diverse manifestations, requiring long-term treatment that can have side effects, particularly in pediatric patients. Nigella sativa (NS) has shown potential for improving SLE symptoms due to its anti-inflammatory and immunomodulatory effects. The aim of this study was to investigate the immunomodulatory effect of N. sativa oil (NSO) on disease activity, T lymphocyte activity and inflammatory cytokine profiles in pediatric SLE patients. A randomized, double-blinded, placebo-controlled clinical trial was conducted at Saiful Anwar Hospital in Malang, Indonesia, from January 2022 to January 2023. Pediatric patients with SLE were randomly assigned to receive either one gram of NSO or a placebo containing starch in capsule form as adjunct therapy alongside their SLE primary treatment. Blood samples were collected before treatment and after eight weeks of daily capsules. Disease activity was assessed using the SLE Disease Activity Index 2000 (SLEDAI-2K); flow cytometry was used to identify T helper lymphocytes, and serum cytokine levels were measured using ELISA. The statistical analysis tests were performed to compare the outcomes between groups at baseline or after the treatment, and within-group comparisons before and after the study period, as appropriate. A total of 32 patients were included in the study. A significant decrease in the SLEDAI-2K score was observed at post-treatment in both the NSO and placebo groups (p<0.001 and p=0.025, respectively). The percentage of T helper 17 (Th17) cells was significantly reduced in both the NSO and placebo groups post-treatment compared to pre-treatment (p=0.026 and p=0.034, respectively). Conversely, the post-treatment percentage of regulatory T (Treg) cells increased significantly in both groups. A significant reduction in interleukin (IL)-2 levels was observed in the NSO and placebo groups at post-treatment compared to pre-treatment (p=0.006 and p=0.046, respectively). Additionally, there were increases in IL-4 and IL-6 serum levels in both groups at post-treatment compared to pre-treatment (p<0.05). This study highlights that although disease activity was not significantly different between NSO and placebo groups, NSO could affect the inflammatory cytokine profiles in pediatric SLE patients.

Health seeking behaviour and diagnostic delays in SLE: A multi-ethnic Malaysian cohort study.

Heterogeneity of the clinical manifestations of systemic lupus erythematosus (SLE) may lead to diagnostic delays. This study is aimed at determining the health-seeking behaviour patterns and factors associated with diagnostic delays in a multi-ethnic SLE cohort in Malaysia. This was a cross-sectional study involving SLE patients who visited our institute between January 2020 and June 2021. A review of the medical records and face-to-face interviews were conducted to obtain sociodemographics, SLE disease characteristics and the intervals from the first symptoms to the diagnosis. Health-seeking behaviours were assessed by asking about the patients' first action during the initial symptoms and were divided into: (i) seeking professional health personnel; (ii) self-treatment; and (iii) the use of the internet as a primary source of information. Diagnostic delays were defined as the interval between initial symptoms and SLE diagnosis of more than 6months. Low-level disease activity state (LLDAS) at 12months was assessed from the medical records. Univariate and multivariate logistic regression analysis was subsequently conducted to determine factors associated with diagnostic delays. Among the 154 patients included in the study, 24% (n = 37) had delayed diagnosis. The delay was significantly higher among the Indian versus Malay versus Chinese (42.9% vs 28% vs 10.8%, p = 0.037). Patients with rash tend to have delayed diagnosis (37.8% vs 22.2%, p = 0.08) while fewer patients with frothy urine had delayed diagnosis (8.1% vs 21.4%, p = 0.09). No significant association was found between health-seeking behaviours and diagnostic delays. The rate of LLDAS at 12months was significantly lower among patients with delayed diagnosis (43.2% vs 70.0%, p = 0.006). Chinese ethnicity remained the only significant factor associated with lesser diagnostic delays in the multivariate analysis, with OR 0.30 (CI 0.09-0.93), p = 0.037. There were ethnic disparities in the early diagnosis of SLE in Malaysia, with Indian patients having a longer interval between the first symptom and diagnosis while the Chinese were associated with lower diagnostic delays. Early diagnosis predicted early attainment of LLDAS, suggesting that prompt recognition of the initial SLE symptoms is important.

The Lived Experiences of Older Adults with Systemic Lupus Erythematosus: Patient Perspectives.

Little is known about perceptions of aging among individuals living with systemic lupus erythematosus (SLE). Gaining this knowledge could help to identify targets for future behavioral interventions aimed at successful aging with SLE. This qualitative study sought to elicit the lived experiences, and essence, of aging from older adults with SLE. We conducted semi-structured interviews with adults ≥65 years of age with SLE seen at a single tertiary center. Qualitative data were analyzed thematically using a phenomenological approach. We collected data on sociodemographic characteristics and disease features prior to each qualitative interview. Among 30 participants with mean age of 71.3 years and mean SLE duration of 26.3 years (range 5 to 62 years), four overarching themes emerged to describe the essence of aging with SLE: SLE and comorbid conditions, cumulative impact of SLE symptoms, SLE disease trajectory, and self-perceptions of aging. Older adults with SLE shared variable aging experiences, including perspectives on multimorbidity and disease trajectory and self-perceptions of aging. We identified both positive and negative self-perceptions of aging, often informed by participants' lived experiences of cumulative impact of SLE symptoms and SLE disease trajectory and underscoring the diversity of their experiences. Understanding self-perceptions of aging in this population could inform development of evidence-based strategies to empower older adults with SLE to harness their positivity and resilience and thus improve health-related outcomes, including health-related quality of life.

Primary Presentation of Systemic Lupus Erythematosus with Pulmonary Embolism: A Case Report

Pulmonary embolism (PE) as the first clinical manifestation of systemic lupus erythematosus (SLE) is an unusual and rare presentation. This case report discusses a 30-year-old male who presented with chest pain and hypoxemia at a hospital in Dubai. Initial workup revealed elevated D-dimer levels and a positive CT pulmonary angiogram confirming PE. The patient’s medical history was unremarkable, except for a recent transient leg discomfort. Upon further investigation, hypoalbuminemia and proteinuria suggested nephrotic syndrome. A thorough autoimmune evaluation revealed elevated anti-dsDNA antibodies, leading to a diagnosis of SLE nephritis. This case emphasizes the necessity of considering SLE as a differential diagnosis for young patients with unexplained thrombotic events, even in the absence of traditional SLE symptoms. Treatment and early recognition are important in managing thrombotic complications in SLE.

Diagnosis of pulmonary lophomoniasis infection in patient with systemic lupus erythematosus; A case report and literature review.

Over the past 30 years, there has been an increasing number of documented human infections associated with the protozoan Lophomonas, specifically Lophomonas blattarum, which is considered a relatively rare infection. These infections are primarily associated with states of immune suppression, including those resulting from corticosteroid therapy. We report a 61-year-old female patient with a 20-year medical history of Systemic lupus erythematosus (SLE) who was admitted due to persistent respiratory symptoms that were unresponsive to treatment. The patient was receiving immunosuppressive therapy for SLE. Upon hospitalization, computed tomography of the lungs revealed the presence of centrilobular nodules exhibiting tree-in-bud patterns, as well as bronchiectasis, predominantly in the middle and lower lobes. Subsequently, the patient underwent bronchoscopy, during which a BAL sample was obtained. Microscopic analysis of the sample indicated the presence of L. blattarum. Clinicians often focus on the primary symptoms of SLE, but they must also consider the risk of severe respiratory complications like lophomoniasis. This condition is critical to address in the management of SLE patients, who are immunosuppressed due to the disease's nature and its treatment.

Factors affecting discrepancies in disease activity evaluation between patients and physicians in systemic lupus erythematosus-The importance of symptoms such as fatigue.

There are often discrepancies in the evaluation of disease activity between patients and physicians in systemic lupus erythematosus (SLE). In this study, we examined the factors that affect those evaluations. Physician visual analogue scale (Ph-VAS), patient VAS (Pt-VAS), Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2k), glucocorticoid (GC) usage and dose, age, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, and three patient-reported outcomes (SLE symptom checklist [SSC], short-form 36 questionnaire [SF-36], and LupusPRO) were obtained from a study performed in 2019 using 225 SLE outpatients of the Kyoto Lupus Cohort at Kyoto University Hospital. Correlations among Ph-VAS, Pt-VAS, or dif (Pt-VAS-Ph-VAS) (Pt-VAS minus Ph-VAS) and other factors were examined. We found a significant discrepancy between Pt-VAS (median 38.0mm) and Ph-VAS (median 18.7mm) scores (p < 0.001). SSC score showed a significant correlation with Pt-VAS and dif (Pt-VAS-Ph-VAS) (p < 0.001). Among SSC items, fatigue showed the most significant correlation with dif (Pt-VAS-Ph-VAS). We also showed that higher dif (Pt-VAS-Ph-VAS) was associated with lower quality of life (QOL) evaluated by SF-36 and LupusPRO. Pt-VAS scores tended to be higher than Ph-VAS scores, and the discrepancy was influenced mainly by fatigue. Higher dif (Pt-VAS-Ph-VAS) was associated with lower patient QOL.

Patient-reported outcome measures for lupus nephritis: content validity of LupusQoL and FACIT-Fatigue

BackgroundLupus nephritis (LN), a severe organ manifestation of systemic lupus erythematosus (SLE), significantly impacts health-related quality of life (HRQoL). Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) and Lupus Quality of Life (LupusQoL) have been validated to measure HRQoL in SLE, but not specifically in LN. Patient-reported symptoms of LN are not well-reported. We assessed the content validity and relevance of these measures in evaluating patients with LN and their LN-related experiences.MethodsThis qualitative, interview-based study enrolled patients with LN from three US sites from a larger, retrospective survey study. The interview comprised an open-ended concept elicitation part and a more structured cognitive part. Concept elicitation was used to identify relevant themes describing the patients’ experiences. Patients were asked to describe their LN-related symptoms, the severity and impact of those symptoms and their satisfaction with treatment. A cognitive interview approach evaluated the appropriate understanding of the items, instructions, and response options and asked patients about their understanding of the FACIT-Fatigue or LupusQoL measures, their relevance to the condition, and any aspects of confusion or need for better clarity of the questionnaires. All interviews were recorded and transcribed. The concept elicitation data were coded, while the cognitive interview data were tabulated to present the participants’ responses next to the interview questions to support the evaluation of their understanding of the questionnaire items.ResultsOverall, 10 patients participated in FACIT-Fatigue and another 10 in LupusQoL interviews; 18 patients were female, 10 were Black (self-reported) and 17 were receiving maintenance treatment for LN with stable disease activity. When patients recalled their symptoms, 670 expressions of varying symptoms were reported. All patients described pain, discomfort, and energy-related symptoms. Urinary frequency and non-joint swelling were most frequently attributed to LN rather than SLE. Patients felt the questions asked in the FACIT-Fatigue and LupusQoL surveys were relevant to their LN experience.ConclusionsThe symptoms reported by patients with LN were consistent with symptoms reported by the overall SLE population. However, patients indicated that some symptoms of LN were more profound than symptoms of SLE alone, affecting a broad range of areas of daily life activity and resulting in a higher burden on their HRQoL. FACIT-Fatigue and LupusQoL demonstrated content relevance as meaningful tools for patients with LN. However, further quantitative data collection is needed to ensure that these patient-reported outcome tools demonstrate good measurement properties in an LN population.

Dihydroartemisinin inhibits follicular helper T and B cells: implications for systemic lupus erythematosus treatment.

Systemic lupus erythematosus (SLE) is a common autoimmune disease, and its pathogenesis mainly involves the aberrant activation of B cells through follicular helper T (Tfh) cells to produce pathogenic antibodies, which requires more effective and safe treatment methods. Dihydroartemisinin (DHA) is the main active ingredient of artemisinin and has immunosuppressive effects. In this study, in vitro experiments confirmed that DHA inhibited Tfh cell induction and weakened its auxiliary function in B cell differentiation; furthermore, DHA directly inhibited B cell activation, differentiation, and antibody production. Furthermore, a mouse model of SLE was established, and we confirmed that DHA significantly reduced the symptoms of SLE and lupus nephritis, and decreased serum immunoglobulin (Ig)G, IgM, IgA, and anti-dsDNA levels. Moreover, DHA reduced the frequencies of total Tfh cells, activated Tfh cells, and B cell lymphoma 6, and interleukin (IL)-21 levels in Tfh cells from the spleen and lymph nodes, as well as the levels of B cells, germinal center B cells, and plasma cells in the spleen, lymph nodes, and kidneys. Additionally, DHA inhibited Tfh cells by blocking IL-2-inducible T cell kinase (ITK) signaling and its downstream nuclear factor (NF)-κB, nuclear factor of activated T cell, and activating protein-1 pathways, and directly inhibited B cells by blocking Bruton's tyrosine kinase (BTK) signaling and the downstream NF-κB and Myc pathways. Overall, our results demonstrated that DHA inhibited Tfh cells by blocking ITK signaling and also directly inhibited B cells by blocking BTK signaling. Therefore, reducing the production of pathogenic antibodies might effectively treat SLE.

Unfavorable Outcomes Associated With Glucocorticoid Use in Current Standard-of-Care Management of Systemic Lupus Erythematosus in Canada.

Our objective was to describe the administration of glucocorticoids (GCs) and characterize its association with organ damage in a longitudinal systemic lupus erythematosus (SLE) cohort over a time period spanning the introduction of biologics in Canada. A retrospective observational study was conducted using data from a large SLE cohort in Canada, including adults without lupus nephritis or central nervous system lupus. Patients were observed from time of entry into the cohort to the last available clinic visit (up to December 31, 2020), with a minimum of 24 months of follow-up. Demographic and clinical characteristics, including average disease activity, treatment administration, and prevalence of organ damage, were examined. Organ damage was stratified by GC administration. A total of 1,255 patients were included. The mean follow-up duration was 10.5 (SD 8.6) years. One hundred eighty-two (15%) patients had organ damage at baseline. More than 80% of patients were prescribed GCs over the follow-up period, almost all patients had long-term GC treatment, and only 5% of patients took any biologics. Organ damage was more frequent in patients with a higher average GC dose and greater years of GC exposure. In this large cohort of patients with SLE, the majority of patients continue to rely on GC for SLE symptom management, with limited administration of biologics. GC administration was correlated with increased irreversible organ damage. Access to novel GC-sparing treatment options is critical to improve long-term outcomes for patients with SLE, especially given the continued reliance on GC despite the introduction of biologics.

The Beneficial Effect of Exercise and Vitamin D Supplementation on Comorbidities Associated with Systemic Lupus Erythematosus

Objective: A multisystem chronic autoimmune illness with recurrent and relapsing episodes that can affect the locomotor system as well as the liver and kidneys is known as systemic lupus erythematosus (SLE). Vitamin D deficiency is thought to play a role in the pathogenesis of SLE. Therefore, our primary aim in this literature review is to determine the role of vitamin D deficiency on SLE symptoms. Our secondary aim is to explain the benefits of exercise on SLE-related comorbidities. Method: A comprehensive literature search on SLE symptoms, biochemistry, and pathophysiology was performed via Google Scholar. The effect of exercise on SLE comorbidities was investigated. Results: Some studies suggest that SLE is caused by environmental and genetic factors. The exact cause of the disease is still unknown, but there is evidence that vitamin D deficiency is associated with SLE symptoms. In addition to drug treatment for locomotor system involvement in SLE patients, physiotherapy applications are also included. In this study, the positive effects of exercise in SLE patients on pain, fatigue, and sleep problems caused by both disease-related and side effects of pharmacological applications used in treatment are reported. Information about the effects of vitamin D deficiency in SLE and how exercise contributes to the improvement of these symptoms is presented. Conclusion: Vitamin D deficiency in the symptoms seen in Systemic Lupus Erythematosus cannot be corrected by vitamin D supplementation alone. At this point, exercise provides possible benefits in correcting vitamin D deficiency. Therefore, exercise has positive effects on SLE comorbidities. Future studies should be planned with the aim of establishing a suitable exercise prescription for SLE.

Lupus progression deteriorates oogenesis quality in MRL/lpr mice.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the activation of the immune response against self antigens. Numerous reproductive complications, including reduced birth rate and complications for the mother and the fetus during pregnancy, have been observed in women with SLE. In the present study, we aimed to investigate the effect of SLE development on oocyte meiosis in lupus-prone mice. Lupus-prone MRL/lpr mice were used for the experiments: disease-free (4weeks of age) and sick (20weeks of age, virgin and postpartum). The immune response was monitored by flow cytometry, ELISpot, ELISA, and histology. Oocytes were analyzed by fluorescence microscopy based on chromatin, tubulin, and actin structures. The lupus-prone MRL/lpr mice developed age-dependent symptoms of SLE with increased levels of various autoantibodies, proteinuria, and renal infiltrates and a tendency for the immune response to worsen with changes in cell populations and the cytokine profile. The number and quality of oocytes were also affected, and the successful pregnancy rate of MRL/lpr mice was limited to only 60%. Isolated oocytes showed severe structural changes in all studied groups. Systemic alterations in immune homeostasis in SLE affect the quality of developing oocytes, which is evident from a young age. The data obtained is in line with the trend of reduced fertility in lupus-prone MRL/lpr mice. The phenomenon can be explained by changes in the microenvironment of the relevant organs and close connection between ovulation and inflammatory processes.

The first clinical experience with selective DNA plasmasorption using the NucleoCapture Device in the treatment of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of unknown etiology characterized by the overproduction of autoantibodies against various components of the nucleus of the patient's own cells with the development of immunoinflammatory tissue damage. In recent years, more and more data have accumulated on the involvement of neutrophils in the development of the clinical symptoms of SLE, and DNA-containing structures and neutrophil extracellular traps (NETs) playing an important role in this process. Effective neutralization of NETs in SLE can be achieved by removing circulating proteins and molecules associated with NETs from the bloodstream by selective plasma sorption of DNA using the NucleoCapture Device.This article describes the case of a patient who underwent three plasma sorption sessions aiming to suppress the activity of SLE. During the therapy, significant positive dynamics were achieved: the SLEDAI-2K index decreased from 32 to 12 points, the number of leukocytes in the blood normalized, renal function improved, and the immunological activity of the disease decreased.

A Scoping Review of the Positive and Negative Bacteria Associated With the Gut Microbiomes of Systemic Lupus Erythematosus Patients.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple systems of the body. Recent research on the gut microbiota dysbiosis associated with SLE patients has gained traction and warranted further exploration. It has not been determined whether the change in the gut microbiota is a cause of SLE or a symptom of SLE. However, based on the physiological and pathophysiological role of the bacteria in the gut microbiome, as levels of the bacteria rise or fall, symptomatology in SLE patients could be affected. This review analyzes the recent studies that examined the changes in the gut microbiota of SLE patients and highlights the correlations between gut dysbiosis and the clinical manifestations of SLE. A systematic search strategy was developed by combining the terms "SLE," "systemic lupus erythematosus," and "gut microbiome." Biomedical Reference Collection, CINAHL, Medline ProQuest, and PubMed Central databases were searched by combining the appropriate keywords with "AND." Only full-text, English-language articles were searched. The articles were restricted from 2013 to 2023. Only peer-reviewed controlled studies with both human and animal trials were included in this scoping review. Review articles, non-English articles, editorials, case studies, and duplicate articles from the four databases were excluded. Various species of bacteria were found to be positively or negatively associated with SLE gut microbiomes. Among the bacterial species increased were Clostridium, Lactobacilli, Streptococcus, Enterobacter, and Klebsiella. The bacterial species that decreased were Bifidobacteria, Prevotella, and the Firmicutes/Bacteroidetes ratio. Literature shows that Clostridium is one of several bacteria found in abundance, from pre-disease to the diseased state of SLE. Lachnospiraceae and Ruminococcaceae are both part of the family of butyrate-producing anaerobes that are known for their role in strengthening the skin barrier function and, therefore, may explain the cutaneous manifestations of SLE patients. Studies have also shown that the Firmicutes/Bacteroidetes ratio is significantly depressed, which may lead to appetite changes and weight loss seen in SLE patients. Based on the established role of these bacteria within the gut microbiome, the disruption in the gut ecosystem could explain the symptomatology common in SLE patients. By addressing these changes, our scoping review encourages further research to establish a true causal relationship between the bacterial changes in SLE patients as well as furthering the scope of microbiota changes in other systems and autoimmune diseases.

Hydroxychloroquine in systemic lupus erythematosus and psychosis. A case report

IntroductionHydroxychloroquine, an antimalarial drug, is an important therapeutic tool in the management of rheumatic diseases such as Systemic Lupus Erythematosus (SLE) due to its anti-inflammatory action. SLE is a chronic autoimmune inflammatory disease that affects the connective tissue of multiple organs. Neuropsychiatric disturbances in SLE are common; however, lupus psychosis is rare, occurring in 2 to 11% of patients. The literature has described the emergence of neuropsychiatric symptoms as an adverse effect of hydroxychloroquine use, with some patients experiencing clinical depression, anxiety, suicidal ideation, and psychotic symptoms.ObjectivesThe aim of this work is to review the available evidence regarding neuropsychiatric symptoms secondary to the use of hydroxychloroquine.Methods The case of a 50-year-old woman diagnosed with SLE, with no other relevant medical history, has been evaluated. She was brought to the emergency department due to paranoid and persecutory ideas, as well as self-referentiality, coinciding with the introduction of hydroxychloroquine in her treatment. She was admitted to the University Hospital of Gran Canaria Doctor Negrín with a diagnostic orientation of a first psychotic episode.ResultsThe presence of neuropsychiatric symptoms in patients diagnosed with SLE is so common that they constitute a diagnostic criterion for the disease. On the other hand, the medications used for therapeutic management of this disease can lead to the emergence of new neuropsychiatric symptoms or exacerbate preexisting neuropsychiatric clinical manifestations.ConclusionsThe study of this case highlights the challenges in establishing a differential diagnosis between primary SLE symptoms that require an increase in hydroxychloroquine and those caused by its own treatment. It underscores the need for further studies to explore the risk of psychiatric symptoms associated with the use of hydroxychloroquine, as well as its impact on the course of underlying mental disorders.Disclosure of InterestNone Declared

Evaluation of Type 2 SLE symptoms in patients with a range of lupus nephritis activity.

Type 2 systemic lupus erythematosus (SLE) symptoms, including fatigue, fibromyalgia, and brain fog, contribute to poor health-related quality of life (HRQoL) in patients with lupus. To test the hypothesis that Type 1 (classical inflammatory lupus) activity is associated with Type 2 SLE activity, we characterized the features of Type 2 SLE in patients with a range of lupus nephritis (LN) activity. This was a cross-sectional study of SLE patients [American College of Rheumatology (ACR) 1997 or Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria] from June 2018 to March 2020. Patients completed the Systemic Lupus Activity Questionnaire (SLAQ) and the Polysymptomatic Distress Scale. Patients were divided into groups based on their renal status. Active nephritis was defined using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) lupus nephritis parameter. Differences across groups were analyzed by Fisher's exact test and ANOVA. In this cohort of 244 patients (93% female, mean age 43years, 58% Black), 10% had active nephritis, 35% had historical nephritis, and 55% never had nephritis (non-nephritis). Active nephritis and non-nephritis patients had a similar burden of Type 2 SLE symptoms, despite a difference in Type 1 SLE activity. Patients with active nephritis had higher Type 2 PGA (Physician Global Assessment) scores and reported more Type 2 SLE symptoms than inactive nephritis patients. Patients with inactive nephritis had the lowest Type 2 SLE activity. While Type 2 SLE symptoms are common in SLE, our findings suggest that patients with active nephritis experience significant Type 2 SLE symptoms that may be ameliorated as nephritis improves. We also observed that non-nephritis patients had a similar burden of Type 2 SLE symptoms as patients with active nephritis, despite having on average lower Type 1 SLE activity. Therefore, the etiology of Type 2 SLE symptoms is likely multifactorial and may be driven by inflammatory and non-inflammatory biopsychosocial factors. Key Points • Patients with active nephritis experienced significant Type 2 symptoms that may be ameliorated as nephritis improves. • Non-nephritis patients had a similar burden of Type 2 SLE symptoms as patients with active nephritis, despite having on average lower Type 1 SLE activity. • Because etiology of Type 2 SLE symptoms is likely multifactorial and may be driven by inflammatory and non-inflammatory biopsychosocial factors.

Time to diagnosis in systemic lupus erythematosus: Associated factors and its impact on damage accrual and mortality. Data from a multi-ethnic, multinational Latin American lupus cohort.

Systemic lupus erythematosus (SLE) often mimics symptoms of other diseases, and the interval between symptom onset and diagnosis may be long in some of these patients. Aims: To describe the characteristics associated with the time to SLE diagnosis and its impact on damage accrual and mortality in patients with SLE from a Latin American inception cohort. Patients were from a multi-ethnic, multi-national Latin-American SLE inception cohort. All participating centers had specialized lupus clinics. Socio-demographic, clinical/laboratory, disease activity, damage, and mortality between those with a longer and a shorter time to diagnosis were compared using descriptive statistical tests. Multivariable Cox regression models with damage accrual and mortality as the end points were performed, adjusting for age at SLE diagnosis, gender, ethnicity, level of education, and highest dose of prednisone for damage accrual, plus highest dose of prednisone, baseline SLEDAI, and baseline SDI for mortality. Of the 1437 included in these analyses, the median time to diagnosis was 6.0months (Q1-Q3 2.4-16.2); in 721 (50.2%) the time to diagnosis was longer than 6months. Patients whose diagnosis took longer than 6months were more frequently female, older at diagnosis, of Mestizo ethnicity, not having medical insurance, and having "non-classic" SLE symptoms. Longer time to diagnosis had no impact on either damage accrual (HR 1.09, 95% CI 0.93-1.28, p = 0.300) or mortality (HR 1.37, 95% CI 0.88-2.12, p = 0.200). In this inception cohort, a maximum time of 24months with a median of 6months to SLE diagnosis had no apparent negative impact on disease outcomes (damage accrual and mortality).

The Type 1 & 2 systemic lupus erythematosus model: Perspectives of people living with systemic lupus erythematosus.

In the new Type 1 & 2 model for systemic lupus erythematosus (SLE), Type 1 SLE represents classic inflammatory manifestations, such as arthritis, while Type 2 SLE encompasses symptoms such as pain and fatigue where the relationship to inflammation is less clear. The objective of this study was to interview individuals living with SLE to determine the content and face validity of the Type 1 & 2 SLE model. We conducted a qualitative study using semi-structured interviews with a purposeful sample of participants who met classification criteria for SLE. Participants were asked to describe their experiences with Type 1 & 2 SLE symptoms and treatments, and they indicated if and how their personal experiences aligned with the Type 1 & 2 SLE model. All interviews were audio-recorded and transcribed; applied thematic analysis identified the most frequent and salient themes. We interviewed 42 participants with SLE. Type 2 SLE symptoms, such as pain and fatigue, were very common, with almost all participants experiencing some Type 2 symptoms at some point during their disease course. Participants described Type 1 SLE symptoms as being acute flares and life-threatening and Type 2 SLE symptoms as "everyday lupus" that affected their daily lives and were a dominant part of their SLE disease experience. Most participants stated they want their rheumatologists to discuss Type 2 symptoms during clinical appointments in order to address their full symptom experience. We demonstrated content and face validity of the Type 1 & 2 SLE model with people living with SLE. Participants in our study largely understood the model and felt it accurately reflected their experience living with SLE. Type 2 SLE symptoms are very common in individuals with SLE and impact patients' quality of life. Using the model to address Type 2 SLE symptoms allows the rheumatologist to incorporate the patient's perspective and provide patient-centered care.

An overlapping case of IgG4-related disease and systemic lupus erythematosus treated with belimumab: a case-based review.

IgG4-related disease (IgG4-RD) is a systemic condition in which IgG4+ plasma cell infiltration and fibrosis cause organ swelling and lead to diverse clinical manifestations. Although IgG4-RD typically responds to glucocorticoids (GCs), relapse during tapering occurs and an early GC-sparing approach might therefore be beneficial. Systemic lupus erythematosus (SLE) is a chronic inflammatory disease with multiple symptoms that is also treated with GCs as a first-line therapy. Recently, belimumab, a recombinant human IgG-1λ monoclonal antibody that inhibits B-cell activating factor, was approved, but reports of use for IgG4-RD are scarce. Here, we present a rare case of IgG4-RD complicated with SLE which was successfully treated with belimumab. A 67-year-old man was diagnosed with IgG4-RD based on a high serum IgG4 level and histopathological findings. Furthermore, he had pericardial effusion on echocardiography, and laboratory tests revealed thrombocytopenia, autoimmune hemolysis, positive anti-nuclear antibodies, positive anti-DNA antibodies, and hypocomplementemia. These data led to an SLE diagnosis. Treatment was started with prednisolone at 40mg/day, plus hydroxychloroquine, which initially improved both the SLE and IgG4-RD symptoms. During the GC tapering, belimumab was added and clinical symptoms resolved completely. Our case and the literature review summarize reported rare overlapping cases of IgG4-RD and SLE and suggest that belimumab is a promising candidate for the treatment of IgG4-RD.

Locus coeruleus tyrosine hydroxylase positive neurons mediated the peripheral and central therapeutic effects of transcutaneous auricular vagus nerve stimulation (taVNS) in MRL/lpr mice

ObjectiveThis study aims to investigate the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on the development of systemic lupus erythematosus (SLE) in MRL/lpr mice. MethodsMRL/lpr mice were treated with taVNS for ten weeks. Locus coeruleus (LC) tyrosine hydroxylase positive (TH+) neurons were selectively lesioned by stereotactic injection of 6-hydroxydopamine (6-OHDA) or selectively activated by chemogenetic methods. Sympathetic denervation was conducted by intraperitoneal injection of 6-OHDA. ResultsTaVNS activated the TH + neurons in LC. TaVNS produced central therapeutic effects by reducing the number of hippocampal microglia, and increasing the number of surviving LC TH+ neurons in MRL/lpr mice. TaVNS also retarded the development of lymphadenectasis and splenomegaly, decreased the proportion of double-negative T (DNT) cells, and alleviated nephritis in MRL/lpr mice. The lesion of LC TH+ neurons eliminated both these central and peripheral therapeutic effects of taVNS, while chemogenetic activation of LC TH+ neurons mimicked most central and peripheral protective effects of taVNS in MRL/lpr mice. Furthermore, taVNS regulated the autonomic nervous system in MRL/lpr mice. ConclusionThis study provides direct evidence that taVNS can retard the development of peripheral and central symptoms of SLE, which is mediated by the LC TH+ neurons.

Transcriptomic features of systemic lupus erythematosus patients in flare and changes during acute in-hospital treatment.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with varying symptoms and multi-organ damage. Relapse-remission cycles often persist for many patients for years with the current treatment. Improved understanding of molecular changes caused by SLE flare and intensive treatment may result in more targeted therapies. RNA sequencing was performed on peripheral blood mononuclear cells (PBMCs) from 65 SLE patients in flare, collected both before (SLE1) and after (SLE2) in-hospital treatment, along with 15 healthy controls (HC). Differentially expressed genes (DEGs) were identified among the three groups. Enriched functions and key molecular signatures of the DEGs were analysed and scored to elucidate the transcriptomic changes during treatment. Few upregulated genes in SLE1 vs HC were affected by treatment (SLE2 vs SLE1), mostly functional in interferon signalling (IFN), plasmablasts and neutrophils. IFN and plasmablast signatures were repressed, but the neutrophil signature remained unchanged or enhanced by treatment. The IFN and neutrophil scores together stratified the SLE samples. IFN scores correlated well with leukopenia, while neutrophil scores reflected relative cell compositions but not cell counts. In-hospital treatment significantly relieved SLE symptoms with expression changes of a small subset of genes. Notably, IFN signature changes matched SLE flare and improvement, while enhanced neutrophil signature upon treatment suggested the involvement of low-density granulocytes (LDG) in disease development.