Incidence Of Systemic Lupus Erythematosus Research Articles

P41 Decoding short stature in a child with lupus nephritis: an unusual association with de la Chapelle syndrome

Abstract Introduction Recent studies have implicated the dysregulation of epigenetic factors in maintaining favourable lyonization of X-chromosome as a plausible putative mechanism in causing high incidence of systemic lupus erythematosus (SLE) in females. This is reflected by the increased risk of SLE in patients with ‘disorders of sex development’ (DSD) such as Klinefelter’s syndrome (47,XXY). de la Chapelle syndrome (46,XX with SRY gene) is another DSD wherein patients resemble males phenotypically with 2 X-chromosomes in their karyotype. Herein, we report the diagnostic and therapeutic challenges in a case of juvenile-onset SLE with refractory lupus nephritis and concomitant association of de la Chapelle syndrome. Case description A 13-year-old boy presented with history of chronic febrile inflammatory polyarthritis involving small and large joints for 6-months. On examination, he had short stature, and swelling, tenderness and restriction of movement of the proximal and distal interphalangeal joints, wrist and shoulder joints of both sides. Investigations revealed elevated erythrocyte sedimentation rate with normal C-reactive protein. Routine urine microscopy examination was suggestive of proteinuria. Further immunological investigations revealed hypocomplementemia, positive anti-nuclear antibody (4+, homogeneous pattern) and elevated titres of anti-double stranded DNA. He was also noted to have positive direct coomb’s test and antiphospholipid antibodies. His renal biopsy was suggestive of lupus nephritis (Class II). Based on the above constellation of clinical and laboratory parameters, a diagnosis of SLE with lupus nephritis (Class II) and musculoskeletal involvement was proffered. He was started on oral prednisolone (2 mg/kg/day followed by taper), hydroxychloroquine (5 mg/kg/day) and sun protective measures. However, persistence of proteinuria after 3-months necessitated addition of mycophenolate mofetil (1200 mg/m2/day) following which his SLE-disease activity went into remission. Notwithstanding the control of SLE-disease activity, there was no improvement in his height after 1-year of follow-up. A pediatric endocrinology consultation for short stature revealed features of idiopathic growth hormone (GH) deficiency and primary hypogonadism. Chromosomal analysis was suggestive of 46,XX karyotype, and fluorescence in situ hybridisation revealed ‘XX’ pattern with SRY gene located on one of the X chromosomes. He was commenced on recombinant GH therapy for 18-months following which his height improved. At 2-years of follow-up, he developed worsening proteinuria. A repeat renal biopsy was suggestive of class-IV lupus nephritis. However, he responded poorly to 6-doses of monthly intravenous cyclophosphamide (500 mg/m2/dose). Considering refractory lupus nephritis, he was commenced on rituximab [(375 mg/m2/dose) at 0 and 2-weeks] following which his proteinuria became passive. He remains well on follow-up. Discussion SLE in DSD has been more frequently described in the context of Klinefelter’s syndrome (47, XXY), implicating the X chromosome as a putative mechanism in its pathogenesis. However, the clinical profile and outcome of SLE in patients with de la Chapelle syndrome has not been explored extensively. de la Chapelle syndrome (46, XX with SRY gene), first described in 1964, is a rare DSD with a reported prevalence of 1/20000 to 1/25000 newborn males. The clinical phenotype includes decreased body height, gynecomastia, maldescended testis and other features of hypogonadism including infertility. Chagnon et al reported the first patient of SLE in de la Chapelle syndrome. Authors described a 19-year-old man who presented with features of SLE since early childhood. His disease was complicated by severe rash, mucositis, arthritis, focal proliferative glomerulonephritis, transaminitis and refractory thrombotic thrombocytopenic purpura, and osteoporosis (including growth failure). In addition, he also had primary hypogonadism with normal GH. Dillon et al also reported another 46, XX male with presence of SRY gene. However, the clinical details including treatment were not elucidated in this paper. Both these patients were phenotypically male due to the presence of SRY gene, similar to the index patient. Our patient’s difficult clinical course with arthritis, growth failure and refractory lupus nephritis, and primary hypogonadism was similar to the patient reported by Chagnon et al. The treatment protocol of SLE in DSD is not well-established. Chagnon et al reported using corticosteroids, hydroxychloroquine, methotrexate, intravenous pulse cyclophosphamide, azathioprine, and plasmapheresis. The index patient was treated similarly; however, due to refractory lupus nephritis, he was also given rituximab. To the best of our knowledge, this is the first report of successful use of anti-CD20 therapy in SLE with DSD such as de la Chapelle syndrome. Key learning points • This case highlights the challenges in diagnosis and management of patients with DSD including de la Chapelle syndrome. The main learning point from this case was that short stature in juvenile-onset SLE in a boy with features of primary hypogonadism warrants further evaluation. As reported in previous literature, this subset of patients may not respond adequately to conventional first-line therapy. The need for escalation of therapy or primary therapy with rituximab in such patients needs further exploration. Another point of concern is using cyclophosphamide, a known drug to have adverse effect on testes, in these patients since it may further compromise testicular function.

Systemic Lupus Erythematosus: An Overview of Pathogenesis, Prevalence, Diagnosis, Classification Criteria, Management, Challenges, and Future Directions

Systemic Lupus Erythematosus (SLE) is a complex, chronic autoimmune disease characterized by widespread inflammation and tissue damage across multiple organ systems. This paper aims to review the SLE pathogenesis, prevalence, diagnosis, classification criteria, management, challenges, and future directions. Scientific literature pertaining to SLE was analyzed through comprehensive searches in specialized academic resources, including PubMed and Google Scholar. This review explores the multifaceted nature of SLE, pathogenesis, which involves a complex interplay of genetic, environmental, and immunological factors leading to the loss of self-tolerance and autoantibody production. The epidemiology section highlights the varying incidence and prevalence of SLE globally. We review current diagnostic approaches, including clinical evaluation and laboratory tests, which are crucial for early and accurate diagnosis. The classification criteria, as outlined by established guidelines, are discussed to provide insight into the diagnostic framework used to identify and categorize SLE. SLE management is briefly addressed, including issues related to disease heterogeneity. Finally, we explore future directions in SLE research, focusing on emerging therapies. Despite advancements, the management of SLE remains challenging, necessitating ongoing research efforts to improve diagnostic precision, therapeutic efficacy, and patient outcomes.

Interplay between polygenic risk score and solar insolation: Implication for systemic lupus erythematosus diagnosis and pathogenesis

ObjectivesThis research elucidates the correlation between solar radiation insolation, polygenic risk score (PRS), and systemic lupus erythematosus (SLE) diagnosis, utilizing genomic, environmental, and clinical data. MethodsWe included 1,800 SLE participants and 1,800 controls from the Taiwan Precision Medicine Initiative, genotyped via the Affymetrix Genome-Wide TWB 2.0 SNP Array. The study employed a SLE-PRS tailored for individuals of Taiwanese ancestry, comprising 27 single nucleotide polymorphisms (SNPs). QGIS computed solar radiation insolation from participants' residences. We employed logistic regression to investigate the associations between SLE-PRS, solar insolation susceptibility, and SLE. Additive and multiplicative interactions were utilized to assess the interactions between solar insolation and SLE-PRS regarding the risk of SLE. ResultsSLE patients showed decreased solar insolation (p < 0.001). The highest decile of SLE-PRS exhibited a statistically significant lower solar insolation 1, 3, 6, and 12 months prior to diagnosis as compared to the lowest decile. Specifically, there were significant differences observed at 1 and 12 months (p = 0.025 and p = 0.004, respectively). It suggests that higher SLE-PRS correlated with reduced solar insolation tolerance. We observed an increase in SLE risk across ascending SLE-PRS percentiles exclusively in the high solar insolation group, not in the low solar insolation group. However, the interaction effect of SLE-PRS and solar insolation on SLE risk is not statistically significant. Compared to the lowest decile, the highest SLE-PRS decile showed a 10.98-fold increase in SLE risk (95 % CI, 3.773–31.952, p < 0.001). High SLE-PRS scores in conjunction with high solar insolation contribute to SLE incidence. ConclusionsOur study unveils the intertwined nature of UV insolation and polygenic risks in SLE. Future studies should explore the preventative potential of robust solar radiation protection for high-risk individuals before the disease onset.

Incidence and prevalence of systemic lupus erythematosus in urban China, 2013–2017: A nationwide population-based study

Systemic lupus erythematosus (SLE) is becoming a growing public health concern due to increasing disease and economic burdens. Epidemiological information about SLE, especially its incidence rate, is limited in developing countries. In the current study, we sought to investigate the incidence, prevalence, and economic burdens of SLE in urban China. We conducted a nationwide population-based cohort study using databases from Urban Employee Basic Medical Insurance and Urban Resident Basic Medical Insurance between 2013 and 2017, covering approximately 300 million residents in 23 provincial regions in China. Incidence rate and prevalence were standardized by age and gender to China’s 2010 national census data. Additionally, we calculated the average annual costs and hospital visit rates. A total of 132,258 SLE patients were identified during the study period, with a mean age of 43.03 years (standard deviation: 15.29 years). Of these patients, 81.33% were women. In 2017, the standardized incidence rate of SLE in China was 14.09 (95% confidence interval (CI), 11.95–16.41) per 100,000 person-years, with a higher incidence in women than in men (26.41 vs. 5.92 per 100,000 person-years). Standardized prevalence in 2017 was 47.61 (41.77–53.83), 94.16 (80.67–108.69), and 17.86 (13.84–22.38) per 100,000 people in the overall, female, and male populations, respectively. The average annual rates of increase in prevalence were 21.50%, 19.72%, and 25.67% from 2013 to 2017 in the overall, female, and male populations, respectively. The age-specific incidence rates peaked at 30–49 years old in women and 40–59 years old in men. SLE incident and prevalent cases were most common in North-West China and less common in southern and eastern China. Distinct variations in incidence rates across different regions are also consistent with the varying levels of ultraviolet radiation exposure in China. Additionally, the average estimated annual per-capita cost was 1599.34 US dollars in SLE patients, with the highest costs observed in adolescent and young adult patients among different age groups. The SLE population in China is rapidly expanding, and younger at onset, especially in women, which has placed significant burdens on China’s healthcare system.

Up-Regulation of microRNA-34a in Women with Systemic Lupus Erythematosus

Systemic Lupus Erythematosus (SLE) is a chronic systemic autoimmune disease with multiple contributing factors. It is characterized by the immune system's inability to tolerate autoantigens such as nuclear antigens. The objective of this study is to evaluate the expression of microRNA-34a in relation to the incidence and occurrence of SLE in Iraqi women using quantitative real-time PCR and to determine its potential relationship with various demographic and laboratory parameters and disease activity. This investigation enrolled 100 healthy controls with a mean age of 31.68 years and 100 SLE patients, all of whom were women with a mean age of 32.85 years and a disease duration of 9.00 (6.75) years. The mean of the Systemic Lupus Erythematosus disease activity index (SLEDAI-2k) score was 10.860±3.275. Erythrocyte sedimentation rate, C-reactive protein, urea, and creatinine were significantly higher (50.00 vs. 10.00 mm/h, 16.70 vs. 0.650 mg/dl, 58.00 vs. 33.00 mg/l, and 1.550 vs. 0.700 mg/l, respectively), while hemoglobin, white blood cells, and Complement 3 and Complement 4 were significantly lower (8.40 vs. 13.00 g/dl, 3.500 vs. 6.800 x 109 /L, 74.00 vs. 130.00 mg/dl, and 10.00 vs. 13.50 mg/dl, respectively) in patients with SLE compared with controls (P≤ 0.001). The analysis of anti-nuclear antibodies (ANA) in patients showed that 89% have ANA and 95% have anti-double-stranded DNA (anti-dsDNA). Also, the findings revealed a significant increase in microRNA-34a expression with fold change (5.19 ±0.48) when compared to the fold change mean in controls (1.00 ±0.00). There is no evidence for any correlation between microRNA-34a fold change and any laboratory or demographic examination of the illness in the present study except for age and BMI. In addition, receiver operating characteristic (ROC) analysis was performed on SLE patients to establish the diagnostic accuracy of microRNA-34a in differentiating SLE patients from controls. The specificity and sensitivity of microRNA-34a were 98% and 100%, respectively. The area under the curve (AUC) was 0.990, and the cutoff point was 1.050. This indicates that the identified microRNA-34a may represent strong biomarkers for SLE disorders.

Fish oil supplementation and risk of incident systemic lupus erythematosus: a large population-based prospective study

BackgroundAlthough fish oil has been considered to have an anti-inflammatory effect and has been proven to play a beneficial role in the incidence of numerous diseases, the association between fish oil supplementation and the risk of systemic lupus erythematosus (SLE) is still unknown. This study aimed at evaluating the correlation between fish oil use and incident SLE in a large population-based prospective cohort.Methods390,277 participants without SLE at baseline from the UK Biobank were enrolled. Fish oil use was ascertained through a touchscreen questionnaire at baseline. The incidence of SLE was identified by the International Classification of Diseases version 10 code in medical records or self-report. Cox proportional hazard models were employed to estimate the association between fish oil use and SLE risk.ResultsFish oil users accounted for 31.47% of participants. During a median follow-up duration of 11.57 years, 141 participants without fish oil use (4.56/100 000 person-years) and 68 participants with fish oil use (4.78/100 000 person-years) developed SLE. In four models with adjustments for different amounts of confounders, there was no significant difference in the risk of SLE between fish oil users and fish oil non-users (all p-values > 0.05). In subgroup analyses, we found that fish oil supplementation was associated with a lower risk of SLE among females with ultraviolet radiation ≥ 3 h/day (hazard ratio: 0.63, 95% confidence interval: 0.40–0.98), which turned insignificant after further adjustment for female-related factors and sun protection measures.ConclusionsNo significant association between fish oil use and overall incident SLE was observed, except in females exposed to prolonged ultraviolet radiation. Subgroup analysis suggested that females exposed to prolonged ultraviolet radiation might benefit from fish oil supplementation in terms of preventing SLE, but it needs to be confirmed in further studies.

Healthcare resource utilization and costs in patients with a newly confirmed diagnosis of lupus nephritis in the United States over a 5-year follow-up period

BackgroundWe aimed to describe healthcare resource utilization (HCRU) and healthcare costs in patients with newly confirmed lupus nephritis (LN) in the United States over a 5-year follow-up period.MethodsThis retrospective, longitudinal cohort study (GSK Study 214102) utilized administrative claims data to identify individuals with a newly confirmed diagnosis of LN between August 01, 2011, and July 31, 2018, based on LN-specific International Classification of Diseases diagnosis codes. Index was the date of first LN-related diagnosis code claim. HCRU, healthcare costs, and incidence of systemic lupus erythematosus (SLE) flares were reported annually among eligible patients with at least 5 years continuous enrollment post-index.ResultsOf 2,159 patients with a newly confirmed diagnosis of LN meeting inclusion and exclusion criteria, 335 had at least 5 years continuous enrollment post-index. HCRU was greatest in the first year post-LN diagnosis across all categories (inpatient admission, emergency room [ER] visits, ambulatory visits, and pharmacy use), and trended lower, though remained substantial, in the 5-year follow-up period. Among patients with LN and HCRU, the mean (standard deviation [SD]) number of ER visits and inpatient admissions were 3.7 (4.6) and 1.8 (1.5), respectively, in Year 1, which generally remained stable in Years 2–5; the mean (SD) number of ambulatory visits and pharmacy fills were 35.8 (25.1) and 62.9 (43.8), respectively, in Year 1, and remained similar for Years 2–5. Most patients (≥ 91.6%) had ≥ 1 SLE flare in each of the 5 years of follow-up. The proportion of patients who experienced a severe SLE flare was higher in Year 1 (31.6%) than subsequent years (14.3–18.5%). Total costs (medical and pharmacy; mean [SD]) were higher in Year 1 ($44,205 [71,532]) than subsequent years ($29,444 [52,310]–$32,222 [58,216]), driven mainly by inpatient admissions (Year 1: $21,181 [58,886]; subsequent years: $7,406 [23,331]–$9,389 [29,283]).ConclusionsPatients with a newly confirmed diagnosis of LN have substantial HCRU and healthcare costs, particularly in the year post-diagnosis, largely driven by inpatient costs. This highlights the need for improved disease management to prevent renal damage, improve patient outcomes, and reduce costs among patients with renal involvement.

Environment and systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a wide range of clinical manifestations and a relapsing-remitting course. SLE pathogenesis is the result of complex interactions between ethnic, genetic, epigenetic, immunoregulatory, hormonal and environmental factors, and several aspects of these multifactorial connections are still unclear. Overall, for the disease development, an environmental trigger may induce immunological dysfunction in genetically predisposed individuals. This review aims to summarise the most relevant data on the impact of environmental factors on the incidence of SLE and on disease activity and damage in patients with an established diagnosis of SLE.

Incidence and risk factors of systemic lupus erythematosus in patients with primary immune thrombocytopenia: a systematic review and meta-analysis.

Immune disorders and autoantibodies has been noted in both primary immune thrombocytopenia (ITP) and systemic lupus erythematosus (SLE). Whether the two disorders are correlated is unclear. The lack of evidence on the incidence of and risk factors for SLE in primary ITP patients poses a challenge for prediction in clinical practice. Therefore, we conducted this study. The protocol was registered with PROSPERO (CRD42023403665). Web of Science, Cochrane, PubMed, and EMBASE were searched for articles published from inception to 30 September 2023 on patients who were first diagnosed with primary ITP and subsequently developed into SLE. Furthermore, the risk factors were analyzed. Study quality was estimated using the Newcastle-Ottawa Scale. The statistical process was implemented using the R language. This systematic review included eight articles. The incidence of SLE during the follow-up after ITP diagnosis was 2.7% (95% CI [1.3-4.4%]), with an incidence of 4.6% (95% CI [1.6-8.6%]) in females and 0 (95% CI [0.00-0.4%]) in males. Older age (OR = 6.31; 95% CI [1.11-34.91]), positive antinuclear antibody (ANA) (OR = 6.64; 95% CI [1.40-31.50]), hypocomplementemia (OR = 8.33; 95% CI [1.62-42.91]), chronic ITP (OR = 24.67; 95% CI [3.14-100.00]), organ bleeding (OR = 13.67; 95% CI [2.44-76.69]), and female (OR = 20.50; 95% CI [4.94-84.90]) were risk factors for subsequent SLE in ITP patients. Patients with primary ITP are at higher risk of SLE. Specific follow-up and prevention strategies should be tailored especially for older females with positive ANA, hypocomplementemia, or chronic ITP. In subsequent studies, we need to further investigate the risk factors and try to construct corresponding risk prediction models to develop specific prediction strategies for SLE.

Pyrexia of unknown origin in a child with chronic diffuse alopecia- A predictor of pediatric systemic lupus erythematosus

ABSTRACT Systemic lupus erythematosus (SLE) is a chronic prototypic autoimmune disorder characterized by the inflammatory and autoimmune reaction leading to protean systemic manifestations. The incidence of childhood-onset SLE has been estimated at an average of 0.6 per 1,00,000 children-years. Childhood-onset SLE has an aggressive course with renal and nervous systems being more involved than in adults. The latest validated Systemic Lupus International Collaborating Clinics (SLICC) criteria, which exhibited a higher sensitivity includes eleven clinical and six immunological items. This criteria has been validated in children. A multidisciplinary therapeutic approach is important due to the complexity of lupus in pediatric patients. We report a case of 12-year-old female child diagnosed as SLE due to its rare occurrence in the pediatric age group.

Environmental exposure to polycyclic aromatic hydrocarbons: An underestimated risk factor for systemic lupus erythematosus onset and progression

ObjectiveTo investigate the link between systemic lupus erythematosus (SLE) incidence and exposure to environmental polycyclic aromatic hydrocarbons (PAH). MethodsA case-control study (ChiCTR2000038187) involving 316 SLE patients and 851 healthy controls (HCs) was executed. Environmental exposure was assessed via a questionnaire, stratified by gender and age (females <35 and ≥35 years, males). Blood samples collected from 89 HCs, 85 inactive, and 95 active SLE patients were used to measure serum benzo[a]pyrene diol epoxide -albumin (BPDE-Alb) adducts and PAH concentrations, indicating long-term and short-term exposure respectively. Intergroup comparisons and statistical analyses were conducted using R version 4.3.1. ResultsDiverse patterns were found in how environmental factors affect SLE onset across different demographics. Lifestyle exposure factors were found to be a stronger determinant of SLE onset than occupational exposure factors in women under 35. Indoor air pollution had a significant impact on SLE incidence, potentially comparable to outdoor air pollution. Lifestyle-related PAH exposure had a greater impact on SLE than occupational PAH exposure. PAH exposure levels progressively increase from HCs to inactive and active SLE patients. Active SLE patients show markedly higher BPDE-Alb levels than HCs. ConclusionsEnvironmental PAH, particularly lifestyle-related, are significant, yet under-recognized, risk factors for SLE. Statement of environmental implicationWe examined the relationship between exposure to environmental polycyclic aromatic hydrocarbons (PAH) and the incidence of systemic lupus erythematosus (SLE). PAH, prevalent in sources such as cigarette smoke, air pollution, and charred food, pose significant health hazards. This study is the first to investigate specific PAH exposure levels in SLE patients. We determined actual PAH exposure levels in both SLE patients and healthy individuals and indicated that long-term PAH exposure biomarker is more reliable for evaluating exposure in non-occupationally exposed groups like SLE, compared to short-term markers. These findings provide valuable insights for future research on similar non-occupationally exposed populations.

Declining Incidence of Systemic Lupus Erythematosus in Norway 1999-2017: Data From a Population Cohort Identified by International Classification of Diseases, 10th Revision Code and Verified by Classification.

The goal of this study was to provide complete, robust data on annual systemic lupus erythematosus (SLE) incidence rates over nearly two decades from the Southeast Norway area (2.9 million inhabitants) and assess accuracy of SLE-specific International Classification of Diseases (ICD) codes for SLE diagnosis. From administrative databases, we identified all cases International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) coded as SLE during 1999 through 2017 in Southeast Norway. We manually reviewed the chart of every case ICD-10 coded as SLE to either confirm or reject SLE diagnosis. Using SLE classification criteria, we classified all cases with confirmed SLE. We estimated annual incidence rates of classified SLE, and subsets, defined by age at diagnosis, sex, and parental country of birth. The chi-square test was applied for linear time-trend analyses of incidence. Among the 3,488 cases ICD-10 coded as SLE, chart reviews confirmed SLE diagnosis in 1,558 (45%), of which 797 had new-onset disease during 1999 through 2017. Annual SLE incidence rates fell during 1999 to 2017. The fall was most pronounced in female persons 50 to 59 years old at diagnosis, in whom incidence fell from 3.4 to 1.1 per 100,000 persons (P trend < 0.001). Concurrent ecological data from the study area showed a 74% reduction in prescriptions of menopausal hormone treatment. Accuracy of ICD-10 codes for incident SLE diagnosis was acceptable in juveniles and young adults (up to 20 years) but otherwise low. In a presumably complete population-based cohort, we identified decreasing incidence of SLE, especially among female persons 50 to 59 years old. Although reasons for declining incidence are not clear, ecological data indicate a possible role of environmental factors, for example, menopausal hormone treatments.

Causal associations of birth body size and adult body size with systemic lupus erythematosus: a bidirectional mendelian randomization study.

Body size is associated with the onset of systemic lupus erythematosus (SLE). However, the evidence for this association is inconclusive. In this study, we aimed to investigate the causal relationship between body size and SLE. We performed a bidirectional Mendelian randomization (MR) analysis that utilized summary statistics sourced from genome-wide association study (GWAS) data obtained from the IEU Open GWAS project website. The inverse variance weighting (IVW) method was used to evaluate the causality, and four additional MR methods were used to supplement the IVW results. Sensitivity analyses were performed using the Cochran's Q test, MR-Egger regression, leave-one-out analysis, and the Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) global test. In the forward direction analysis, the IVW model demonstrated that birth weight (odds ratio (OR), 1.811; 95% confidence interval (CI), 1.174-2.793; p < 0.05) and adult height (OR, 1.225; 95% CI, 1.046-1.434; p < 0.05) were positively associated with SLE. Four additional MR scans were performed parallel to the IVW results. Conversely, SLE was a weak causal factor for increased height (OR, 1.010; 95% CI, 1.002-1.018; p < 0.05) using the IVW method. Heterogeneity, MR-Egger intercept, and leave-one-out analyses indicated that the results were robust. The MR-PRESSO suggested the presence of pleiotropy. Following the exclusion of instrumental variables (IVs) inducing pleiotropy, subsequent MR analysis yielded consistent results, thereby reinforcing the robustness of our findings. Positive causal associations were observed between birth weight, adult height, and SLE incidence. In the reverse analysis, SLE was a weak causal factor for adult height.

Association of microRNA-155 gene polymorphism and the incidence of systemic lupus erythematosus in Iraqi patients

An intricate, multisystemic autoimmune disease that affects multiple organs is known as systemic lupus erythematosus, or SLE. Alterations in genetic material contribute to the development of SLE. The present work aims to investigate the association of genetic variants of microRNA-155 (miR-155) that are essential in the pathogenesis of SLE. A case-control study was conducted with40 female patients and 40 healthy individuals as control group who were from the Medical City/Baghdad Teaching Hospital. The molecular study of miR-155 was performed by polymerase chain reaction using uniquely designed primers followed by sanger sequencing the results showed that wild type was present in all 80 samples. This study also detected two SNPs (rs190708267 and rs1547354) under the control group. According to NCBI, the SNPs detected are not related to any disease, but may be protective factors in healthy individuals.

Intestinal permeability and inflammatory features of juvenile age correlate with the eventual systemic autoimmunity in lupus-prone female SWR × NZB F1 (SNF1) mice.

The incidence of systemic lupus erythematosus (SLE) is about nine times higher in women than in men, and the underlying mechanisms that contribute to this gender bias are not fully understood. Previously, using lupus-prone (SWR × NZB)F1 (SNF1) mice, we have shown that the intestinal immune system could play a role in the initiation and progression of disease in SLE, and depletion of gut microbiota produces more pronounced disease protection in females than in males. Here, we show that the gut permeability features of lupus-prone female SNF1 mice at juvenile ages directly correlate with the expression levels of pro-inflammatory factors, faecal IgA abundance and nAg reactivity and the eventual systemic autoantibody levels and proteinuria onset. Furthermore, we observed that the disease protection achieved in female SNF1 mice upon depletion of gut microbiota correlates with the diminished gut inflammatory protein levels, intestinal permeability and circulating microbial DNA levels. However, faecal microbiota transplant from juvenile male and females did not result in modulation of gut inflammatory features or permeability. Overall, these observations suggest that the early onset of intestinal inflammation, systemic autoantibody production and clinical stage disease in lupus-prone females is linked to higher gut permeability in them starting at as early as juvenile age. While the higher gut permeability in juvenile lupus-prone females is dependent on the presence of gut microbes, it appears to be independent of the composition of gut microbiota.

HLA-DR genotypes in patients with systemic lupus erythematosus in Taiwan.

Different human leukocyte antigen (HLA)-DR genotypes have been known to be associated with the risk of development of systemic lupus erythematosus (SLE) in different populations, although Lu et al. have reported previously that no correlation exists between the HLA-DR genotype and disease manifestation in SLE patients in Taiwan. We investigated the effects different HLA-DR genotypes had on SLE incidence in Taiwanese patients as to whether risk alleles were associated with different clinical manifestations, and the effects risk alleles had on the age of disease onset. Two hundred thirty-four SLE patients and 346 healthy controls were enrolled. HLA-DR genotyping was performed with the HLA FluoGene DRDQ kit for each subject. Chi-square tests and t tests were performed for statistical analysis. HLA-DR2 was significantly more frequently found in SLE patients than in controls (odds ratio [OR] = 2.05, 95% CI, 1.44-2.92, p < 0.001). Notably, HLA-DR6 appeared to trend toward negative correlation with SLE, whereas HLA-DR8 appeared to trend toward positive correlation. HLA-DR2 patients had an earlier onset of disease as well as a higher prevalence of oral ulcer, avascular necrosis of bone, and renal involvement (lupus nephritis). HLA-DR2 was associated with SLE susceptibility in this Taiwanese population as well as lower age of disease onset and more severe clinical manifestations.

Epidemiology and Damage Accrual of Systemic Lupus Erythematosus in Central Sweden: A Single-Center Population-Based Cohort Study Over 14 Years From Östergötland County.

Variations in prevalence and incidence of systemic lupus erythematosus (SLE) within a geographically defined area of central Sweden over a time period of 14 years were examined. Longitudinal differences in disease activity, laboratory test results, and damage accrual were investigated. Adults (aged ≥18 years) residing in Östergötland County between 2008 and 2021 (mean adult population: 357,000 citizens) with confirmed SLE were identified and followed prospectively until death, December 31, 2021, or emigration. We estimated annual incidence per 100,000 inhabitants stratified by sex and age. Linear regression with year of diagnosis as the outcome assessed whether each clinical measurement at diagnosis varied over time. Prevalence on December 31, 2021, was 71.5 of 100,000 (87% female). One hundred twenty-six new cases were identified during the study period, yielding a mean annual incidence of 3.0 of 100,000 inhabitants; this was higher in females (4.8/100,000) than in males (1.2/100,000). Mean age at diagnosis was 43.7 years (SD 17.3). Age at diagnosis and disease activity measures increased over the calendar year of diagnosis (P < 0.05) whereas disease manifestations, including lupus nephritis, did not vary significantly. Accrual of organ damage was demonstrated over time since diagnosis and stratified by sex, lupus nephritis, and corticosteroid-related damage. Approximately 40% developed damage within 5 years. SLE prevalence and incidence estimates remained constant over 14 years, and disease phenotypes at SLE onset were similar. SLE was diagnosed also among older individuals with a smaller female-to-male ratio. Estimates of prevalence and incidence were comparable to previous Scandinavian reports but lower than observed in registry data from the US and the UK.

Incidence and prevalence of systemic lupus erythematosus in New Zealand from the national administrative datasets.

This study aims to provide updated data on the incidence and prevalence of systemic lupus erythematosus (SLE) in New Zealand and to examine the difference between ethnic groups. We identified the SLE cases from the national administrative datasets. The date of first identification of SLE was the earliest date of a related inpatient event or the earliest date of a related outpatient event. The crude incidence and prevalence of SLE in 2010-2021 were estimated by gender, age group and ethnicity. The WHO (World Health Organization) age-standardised rate (ASR) of incidence and prevalence of SLE was calculated, after stratifying the cases by ethnicity and gender. The average ASR of incidence and prevalence of SLE in 2010-2021 was 2.1 and 42.1 per 100,000 people in New Zealand. The average ASR of incidence for women was 3.4 per 100,000 for women and 0.6 for men. It was highest for Pacific women (9.8), followed by Asian women (5.3) and Māori women (3.6), and was lowest for Europeans/Others (2.1). The average ASR of prevalence was 65.2 per 100,000 for women and 8.5 for men. It was highest for Pacific women (176.2), followed by Māori women (83.7) and Asian women (72.2), and was lowest for Europeans/Others (48.5). The ASR of prevalence of SLE has been increasing slightly over time: from 60.2 in 2010 to 66.1 per 100,000 in 2021 for women and from 7.6 in 2010 to 8.8 per 100,000 in 2021 for men. The incidence and prevalence of SLE in New Zealand were comparable to the rates in European countries. Pacific people had the highest incidence and prevalence of SLE, more than three times the rates for Europeans/others. The high incidence of SLE in Māori and Asian people also has implications for the future as these populations increase as a proportion to the total population.

Clinical characteristics of palmoplantar discoid lupus erythematosus: A multicenter retrospective review of 43 patients

AbstractBackgroundPalmoplantar discoid lupus erythematosus (ppDLE) is a rare manifestation of chronic cutaneous lupus erythematosus that can result in painful, hyperkeratotic, and/or erosive lesions on the palms and soles. Despite this penchant to cause significant morbidity, the natural history of ppDLE and its response to conventional treatment approaches remain poorly understood.ObjectivesTo characterize the initial presentation, treatment response, and association with systemic lupus erythematosus (SLE) of ppDLE.MethodsWe performed an International Classification of Diseases (ICD‐9 and ICD‐10) code and natural‐language query for medical records from Brigham and Women's Hospital and Massachusetts General Hospital to identify all cases of ppDLE based on biopsy and/or expert opinion from January 2000 through October 2022. Demographics, clinical features, and treatment data were analysed.ResultsForty‐three patients (median age, 29.5 years [range, 8−70 years]; 36 female [83.7%]) with ppDLE were identified. Mean time from initial clinical presentation of ppDLE symptoms to diagnosis was 14.5 months (n = 34). Of the 43 patients, 74.4% developed coexistent SLE. A mean of 5.9 (standard deviation, 2.7) lines of therapy were required to achieve control of ppDLE, with the majority of patients requiring the initiation of at least two concomitant systemic medications.ConclusionsHerein, we present the largest cohort of patients with ppDLE in the literature to date. Despite a high incidence of coexistent SLE, patients experienced lengthy diagnostic delays. Even with appropriate diagnosis, an overwhelming trend towards treatment‐refractory disease was observed.

Antibodies to histone in the pediatric population: a retrospective chart review

BackgroundAntibodies to histone have been associated in the adult literature with systemic lupus erythematosus(SLE) and drug induced lupus(DILE). Little data is available regarding the spectrum of pathology that antibodies to histone encompass in the pediatric population. Prior studies suggest an association with SLE, juvenile idiopathic arthritis(JIA), uveitis and linear scleroderma.MethodsPatient charts were reviewed that contained positive anti-histone antibody testing during a consecutive three year period. Patient diagnosis along with the presence of: anti-histone antibody titer, ANA, and the presence of other autoantibodies to SSA, SSB, Sm, RNP, dsDNA and chromatin were obtained. The frequency of SLE, JIA and DILE was further investigated in specific subsets.Results139 individual charts were reviewed containing 41 different diagnoses. The most common diagnosis was hypermobility arthralgia with 22 patients. The most frequent rheumatologic diagnosis was JIA(nonsystemic) with 19. 13 patients in this study were diagnosed with SLE and 2 with DILE. 18 patients had other autoantibody production, of these, 11 had SLE or DILE. Only one of 62 patients with a weak antihistone antibody titer(1.0-1.5) was diagnosed with SLE. When strong titers are present(> 2.5), the antihistone antibody test was associated with a greater than 50% incidence of an underlying rheumatologic disease and ten times higher incidence of SLE than a weak titer. In regards to the frequency of SLE, there was a statistically significant difference between weak and moderate titers and between weak and strong titers.ConclusionThe presence of anti-histone antibody was observed in a variety of diagnoses in the pediatric population. Overall, the presence of anti-histone antibodies appears to have poor diagnostic utility for any specific condition. However, diagnostic utility for SLE does appear to improve with higher titers, when combined with other autoantibody positivity. Strength of titer did not appear to be a factor for JIA, but was the most frequently observed rheumatologic disease in this study.