Adult Systemic Lupus Erythematosus Research Articles

Impact of disease activity patterns on health-related quality of life (HRQoL) in patients with systemic lupus erythematosus (SLE)

ObjectiveTo assess the impact of different disease activity patterns—long quiescent (LQ), chronically active (CA) and relapsing-remitting (RR)—on health-related quality of life (HRQoL) in a cohort of patients with systemic lupus...

Psychological impact of life events in systemic lupus erythematosus patients - Differences between flares and remission.

Stress has been linked to worsening symptoms and increased disease activity in patients with Systemic lupus erythematosus (SLE). Life-events are individual stress points, and there is conflicting evidence regarding their role in SLE activity and disease perception. Adult SLE patients were recruited for the study. Clinical and laboratory features of SLE were recorded, and previous diagnosis of anxiety or depression were retrieved from patients' electronic charts. Flares were defined by the Systemic Lupus Erythematosus Disease Activity (SLEDAI) flare Index, and flares during the previous year were documented. During a routine visit, they completed validated Portuguese translations of the 10-item Perceived Stress Scale (PSS-10), Hospital Anxiety and Depression Scale (HADS) and Life Experience Survey (LES) for the previous year. A total of 47 female SLE patients were recruited. Ten patients (21.3%) had experienced recent flares. Patients with recent flares reported fewer life events, with lower positive, negative, and total weightings sums compared to those without recent flares. Although 42.2% of patients perceived pathological levels of stress in the previous month, 48.9% had anxiety symptoms, and 34% were at high risk for an anxiety disorder, these psychometric measures did not differ significantly between the recent flare and no-flare groups. There is a high prevalence of pathological levels of stress among SLE patients. SLE patients with recent flares report less psychological impact from life events, both positive and negative, independent of other psychological or pharmacological factors.

Serum Levels of Interleukin-2 in a Cohort of Egyptian Systemic Lupus Erythematosus Patients with Glomerulonephritis

Abstract Background Lupus nephritis is a serious complication of systemic lupus erythematosus(SLE).It is clinically evident in 50-60% of SLE patients, and it is histologically evident in most SLE patients. Defective Interleukin-2(IL-2) production contributes to the unbalanced immune system in SLE. Aim of the Work To evaluate the relationship between serum IL-2 level and renal involvement in SLE patients. Patients and Methods 60 adult SLE patients were studied. SLE Disease Activity Index-2000 (SLEDAI-2K) and serum IL-2 level by ELISA were assessed. Results Patients were (93.3%) females and (6.7%) males; their ages (19- 58 years) with median disease duration 4 (0.25-24years). The median IL-2 level was significantly lower in SLE patients with nephritis 25.5 ng/L (5-90 ng/L) than in patients without nephritis 53.5 ng/L (29-165 ng/L) (p ≤ 0.001). There was negative correlation between serum IL-2 and serum creatinine (r= -0.494 p ≤ 0.001) and between serum IL-2 and protein/creatinine ratio (r=-0.512 p ≤ 0.001). Although there was no relationship between SLE disease activity and serum IL-2; the level of serum IL-2 was higher with mild SLE disease activity (45-60 ng/L) followed by moderate activity (15-135 ng/L) and the lowest with high disease activity (5-165 ng/L). An increase in s.creatinine and a decrease in S.IL-2 had an independent effect on increasing probability of occurrence of nephritis in SLE patients (p < 0.01). Conclusion Serum IL-2 might have an important role in predicting the occurrence of lupus nephritis in SLE.

Does the esv3587290 Copy Number Variation in the VANGL1 Gene Differ as a Genetic Factor for Developing Nephritis in Mexican Childhood-Onset Systemic Lupus Erythematosus Patients?

A ~3-kb deletion-type DNA copy number variation (CNV, esv3587290) located at intron 7 of the VANGL1 gene (1p13.1, MIM*610132) has been proposed as a genetic factor in lupus nephritis (LN) development in adult systemic lupus erythematosus (SLE) patients across European-descent populations, but its replication in other ethnicities has been inconsistent and its association with LN in childhood-onset SLE (cSLE) remains unknown. Here, we performed an exploratory association study in a sample of 66 unrelated cSLE Mexican patients (11 males, 55 females; ages 7.8 to 18.6 years). Two stratified groups were compared: cSLE patients with (N = 39) or without (N = 27) LN, as diagnosed by renal biopsy (N = 17), proteinuria (N = 33), urinary protein-creatinine ratio > 0.2 (N = 34), and erythrocyturia and/or granular casts in urinary sediment (N = 16). For esv3587290 CNV genotyping, we performed an end-point PCR assay with breakpoint confirmation using Sanger sequencing. We also determined the allelic frequencies of the esv3587290 CNV in 181 deidentified ethnically matched individuals (reference group). The obtained genotypes were tested for Hardy-Weinberg equilibrium using the χ2 test. Associations between LN and esv3587290 CNV were tested by calculating the odds ratio (OR) and using Pearson's χ2 tests, with a 95% confidence interval and p ≤ 0.05. The esv3587290 CNV allele (OR 0.108, 95% CI 0.034-0.33, p = 0.0003) and the heterozygous genotype (OR 0.04, 95% CI 0.119-0.9811, p = 0.002) showed a significant protective effect against LN development. Finally, we characterized the precise breakpoint of the esv3587290 CNV to be NG_016548.1(NM_138959.3):c.1314+1339_1315-897del in our population. This report supports the notion that a broad genetic heterogeneity underlies the susceptibility for developing LN.

An interactive web application for exploring systemic lupus erythematosus blood transcriptomic diversity.

In the field of complex autoimmune diseases such as systemic lupus erythematosus (SLE), systems immunology approaches have proven invaluable in translational research settings. Large-scale datasets of transcriptome profiling have been collected and made available to the research community in public repositories, but remain poorly accessible and usable by mainstream researchers. Enabling tools and technologies facilitating investigators' interaction with large-scale datasets such as user-friendly web applications could promote data reuse and foster knowledge discovery. Microarray blood transcriptomic data from the LUPUCE cohort (publicly available on Gene Expression Omnibus, GSE49454), which comprised 157 samples from 62 adult SLE patients, were analyzed with the third-generation (BloodGen3) module repertoire framework, which comprises modules and module aggregates. These well-characterized samples corresponded to different levels of disease activity, different types of flares (including biopsy-proven lupus nephritis), different auto-antibody profiles and different levels of interferon signatures. A web application was deployed to present the aggregate-level, module-level and gene-level analysis results from LUPUCE dataset. Users can explore the similarities and heterogeneity of SLE samples, navigate through different levels of analysis, test hypotheses and generate custom fingerprint grids and heatmaps, which may be used in reports or manuscripts. This resource is available via this link: https://immunology-research.shinyapps.io/LUPUCE/. This web application can be employed as a stand-alone resource to explore changes in blood transcript profiles in SLE, and their relation to clinical and immunological parameters, to generate new research hypotheses.

Subclinical choroidal involvement in Systemic Lupus Erythematosus.

To assess the choroidal status of Systemic Lupus Erythematosus (SLE) patients using Optical Coherence Tomography (OCT) and OCT-Angiography. SLE patients with disease duration < 10years, no disease activity and no ocular involvement were recruited and cross-sectionally evaluated. A demographically similar cohort of healthy subjects was used for comparison. The main outcome is choroidal vascularity index (CVI). As secondary outcomes, choriocapillaris parameters and choroidal thickness (CT) were evaluated. Forty eyes of 40 subjects (20 SLE patients and 20 healthy subjects) were studied with a mean ± SD age of 36.7 ± 9.9years. In the SLE group, the mean ± SD duration of disease was 7.35 ± 2.21years. Increased CVI was found in the SLE group (p = 0.022). Considering the choriocapillaris, SLE patients presented a lower number (p = 0.037) and a smaller total area (p = 0.041) of signal voids. No differences between groups were found in CT. For SLE patients, CT at subfoveal, temporal and inferior locations presented a negative moderate correlation with disease duration. A strong correlation between choriocapillaris parameters and age was demonstrated for both groups. This study provides evidence of subclinical choroidal changes in adult SLE patients with inactive disease and no overt ocular manifestation. Increased CVI and fewer and smaller flow voids in choriocapillaris with normal CT suggest increased choroidal vascularity in SLE.

Gender-driven thyroid dysfunction in systemic lupus erythematosus patients: Clinical significance of an overlooked association and global stance

Aim of the workThis study aimed to determine the association of thyroid dysfunction in systemic lupus erythematosus (SLE) patients. Patients and methodsOut of a cohort including 312 adult SLE patients those with thyroid dysfunction (n = 53) were further evaluated. The medical history, clinical examination, laboratory investigations and medications received were recorded. The SLICC damage index (SLICC-DI) was assessed. ResultsThyroid dysfunction formed 17 % of the patients and their mean age was 39.5 ± 11.5 years and disease duration 5.6 ± 3.3 years were comparable to those without thyroid disorder, however female gender was predominantly higher (F:M 52:1 vs 6.2:1, p < 0.0001). The frequency of thyroid dysfunction was alike in Saudi (16 %) and non-Saudi (17.9 %) patients (p = 0.66). The majority of cases (96.2 %) had hypothyroidism, one with autoimmune thyroiditis, while only 2 (3.8 %) had hyperthyroidism. There was a significantly increased frequency of associated neuropsychiatric manifestations (64.2 % vs 45.2 %;p = 0.012), and hematological involvement (32.1 % vs 14.3 %; p = 0.011) and less complement (C4) consumption (15.1 % vs 23.6 %; p = 0.048) in those with thyroid dysfunction compared to those without. The frequency of anti-double stranded deoxyribonucleic acid (anti-dsDNA) positivity tended to be higher (71.7 % vs 66.8 %) and its titre significantly lower (316.3 ± 319.8 IU/ml vs 461.3 ± 459.1; p = 0.013). The SLICC-DI and mortality rate were comparable between groups. Only the presence of proteinuria inversely significantly correlated with the level of T4 (r = -0.31, p = 0.007). ConclusionThyroid dysfunction forms a notable percentage of SLE patients with a prominent female gender propensity. The significant relation of thyroid disorders to neuropsychiatric manifestations, hematological involvement, C4 consumption and anti-dsDNA deserves recognition.

Saudi National Clinical Practice Guidelines for Management of Adult Systemic Lupus Erythematosus.

To provide evidence-based clinical practice recommendations for managing Systemic Lupus Erythematosus (SLE) in Saudi Arabia. This EULAR-adapted national guideline in which a multidisciplinary task force utilized the modified Delphi method to develop 31 clinical key questions. A systematic literature review was conducted to update the evidence since the EULAR publication. After reaching a consensus agreement, two rounds of voting and group discussion were conducted to generate consolidated recommendations/statements. A significant number of patients in Saudi Arabia experience delays in accessing rheumatologists, highlighting the significance of timely referral to SLE specialists or rheumatologists to ensure accurate diagnosis and prompt treatment. The primary goal of Glucocorticoid (GC) therapy in SLE patients is to establish disease control with a minimum dose and duration. Steroid-sparing agent utilization facilitates steroid-sparing goals. Hydroxychloroquine is recommended for all SLE patients, though physicians must carefully monitor toxicity and prioritize regular medication adherence assessment. SLE management during pregnancy starts from preconception time by assessing disease activity, major organ involvement, hypercoagulability status, and concomitant diseases that may negatively impact maternal and fetal outcomes. Multidisciplinary care with close monitoring may optimize both maternal and fetal outcomes. For patients with antiphospholipid antibodies, low-dose aspirin prophylaxis is recommended. Also, Long-term anticoagulant medications are fundamental to prevent secondary antiphospholipid syndrome due to high thrombosis recurrence. This Saudi National Clinical Practice guidelines for SLE management provide evidence-based recommendations and guidance for healthcare providers in Saudi Arabia who are managing patients with SLE. These guidelines will help to standardize healthcare service, improve provider education, and perhaps lead to better treatment outcomes for SLE patients.

Polygenic Risk Score Predicts Earlier-Onset Adult Systemic Lupus Erythematosus and First-Year Renal Diseases in a Taiwanese Cohort

ObjectivesThis study aimed to develop a predictive model using polygenic risk score (PRS) to forecast renal outcomes for adult systemic lupus erythematosus (SLE) in a Taiwanese population.MethodsPatients with SLE (n=2782)...

Obesity and tobacco smoking are independently associated with poor patient-reported outcomes in SLE: a cross-sectional study

We investigated associations of obesity and tobacco smoking with health-related quality of life (HRQoL), pain, fatigue, and functional impairment in systemic lupus erythematosus (SLE). Furthermore, we explored whether there was an effect modification between these two factors. We included adult SLE patients from the Linköping University Hospital (n = 325) in the present cross-sectional analysis. We further included population-based controls and performed cardinality matching to balance age and sex distributions with cases (n = 224). HRQoL was assessed with the EQ-5D index score; pain, fatigue, and overall SLE-related health state with visual analogue scales (VAS; 0 [best] to 100 [worst]); and functional impairment with the HAQ-DI. Unacceptable outcomes were defined as VAS scores corresponding to the 90th percentile derived from the matched controls. SLE patients reported worse scores than controls in all measures, and approximately 30% experienced unacceptable outcomes. When compared with normal-weight, obese SLE patients reported lower HRQoL, and greater functional impairment and risk of unacceptable pain (OR: 3.2; 95% CI 1.6–6.7) and fatigue (OR: 2.1; 95% CI 1.0–4.3). Similarly, the current smokers reported higher levels of functional impairment and a greater risk of unacceptable pain (OR: 3.8; 95% CI 1.8–8.2) and fatigue (OR: 2.8; 95% CI 1.3–5.9) than never smokers. The associations were independent of age, sex, disease duration, disease activity, and organ damage. There was no evidence of a synergistic effect between increased BMI and smoking on any outcome. In summary, obesity and smoking are risk factors for unacceptable patient-reported outcomes in SLE, regardless of clinical activity.

Predictors of Organ Damage in Systemic Lupus Erythematosus in the Asia Pacific Region: A Systematic Review.

Irreversible organ damage is common in patients with systemic lupus erythematosus (SLE). Despite evidence of increased prevalence and severity of SLE in Asia Pacific, organ damage is less well studied in this region. This systematic review aims to identify predictors of organ damage in SLE in the Asia Pacific region. We searched Medline, PubMed, Embase, and Web of Science for observational studies on organ damage in adult patients with SLE in Asia Pacific from August 31, to September 5, 2022. Study selection and data extraction were completed by two independent reviewers using Covidence systematic review software. Risk of bias was assessed using the Newcastle-Ottawa Scale and Joanna Briggs Institute tool. Significant results from univariable and multivariable analyses were synthesized from included studies. Thirty-eight eligible studies were selected from 1999 to 2022; 22 (58%) of these reported organ damage at study enrollment and 19 (50%) reported damage accrual, as measured by the Systemic Lupus International Collaborating Clinic/American College of Rheumatology Damage Index. Factors predictive of organ damage included older age, glucocorticoid use, longer disease duration, and disease activity. Lupus nephritis was a risk factor for renal and overall damage accrual. Hydroxychloroquine was protective against overall organ damage. Predictors of organ damage in SLE in Asia Pacific are similar to other regions. Although glucocorticoid use is a modifiable risk factor for organ damage, the impact of immunosuppressives and biologic therapies needs further investigation. Effective strategies in early disease are needed to minimize initial organ damage as it predicts subsequent damage accrual.

Ion channel TRPV2 is critical in enhancing B cell activation and function.

The function of transient receptor potential vanilloid (TRPV) cation channels governing B cell activation remains to be explored. We present evidence that TRPV2 is highly expressed in B cells and plays a crucial role in the formation of the B cell immunological synapse and B cell activation. Physiologically, TRPV2 expression level is positively correlated to influenza-specific antibody production and is low in newborns and seniors. Pathologically, a positive correlation is established between TRPV2 expression and the clinical manifestations of systemic lupus erythematosus (SLE) in adult and child SLE patients. Correspondingly, mice with deficient TRPV2 in B cells display impaired antibody responses following immunization. Mechanistically, the pore and N-terminal domains of TRPV2 are crucial for gating cation permeation and executing mechanosensation in B cells upon antigen stimulation. These processes synergistically contribute to membrane potential depolarization and cytoskeleton remodeling within the B cell immunological synapse, fostering efficient B cell activation. Thus, TRPV2 is critical in augmenting B cell activation and function.

Single-cell analysis with childhood and adult systemic lupus erythematosus

Patients with systemic lupus erythematosus (SLE), a heterogeneous and chronic autoimmune disease, exhibit unique changes in the complex composition and transcriptional signatures of peripheral blood mononuclear cells (PBMCs). While the mechanism of pathogenesis for both childhood-onset SLE (cSLE) and adult-onset SLE (aSLE) remains unclear, cSLE patients are considered more unpredictable and dangerous than aSLE patients. In this study, we analysed single-cell RNA sequencing data (scRNA-seq) to profile the PBMC clusters of cSLE/aSLE patients and matched healthy donors and compared the PBMC composition and transcriptional variations between the two groups. Our analysis revealed that the PBMC composition and transcriptional variations in cSLE patients were similar to those in aSLE patients. Comparative single-cell transcriptome analysis between healthy donors and SLE patients revealed IFITM3, ISG15, IFI16 and LY6E as potential therapeutic targets for both aSLE and cSLE patients. Additionally, we observed that the percentage of pre-B cells (CD34-) was increased in cSLE patients, while the percentage of neutrophil cells was upregulated in aSLE patients. Notably, we found decreased expression of TPM2 in cSLE patients, and similarly, TMEM150B, IQSEC2, CHN2, LRP8 and USP46 were significantly downregulated in neutrophil cells from aSLE patients. Overall, our study highlights the differences in complex PBMC composition and transcriptional profiles between cSLE and aSLE patients, providing potential biomarkers that could aid in diagnosing SLE.

Childhood-onset systemic lupus erythematosus (cSLE) and malignancy: a nationwide multicentre series review

BackgroundIncreased malignancy frequency is well documented in adult-systemic lupus erythematosus (SLE), but with limited reports in childhood-onset SLE (cSLE) series. We explored the frequency of malignancy associated with cSLE, describing clinical and demographic characteristics, disease activity and cumulative damage, by the time of malignancy diagnosis.MethodA retrospective case-notes review, in a nationwide cohort from 27 Pediatric Rheumatology centres, with descriptive biopsy-proven malignancy, disease activity/damage accrual, and immunosuppressive treatment were compiled in each participating centre, using a standard protocol.ResultsOf the 1757 cSLE cases in the updated cohort, 12 (0.7%) developed malignancy with median time 10 years after cSLE diagnosis. There were 91% females, median age at cSLE diagnosis 12 years, median age at malignancy diagnosis 23 years. Of all diagnosed malignancies, 11 were single-site, and a single case with concomitant multiple sites; four had haematological (0.22%) and 8 solid malignancy (0.45%). Median (min–max) SLEDAI-2 K scores were 9 (0–38), median (min–max) SLICC/ACR-DI (SDI) score were 1 (1–5) Histopathology defined 1 Hodgkin's lymphoma, 2 non-Hodgkin's lymphoma, 1 acute lymphoblastic leukaemia; 4 gastrointestinal carcinoma, 1 squamous cell carcinoma of the tongue and 1 anal carcinoma; 1 had sigmoid adenocarcinoma and 1 stomach carcinoid; 3 had genital malignancy, being 1 vulvae, 1 cervix and 1 vulvae and cervix carcinomas; 1 had central nervous system oligodendroglioma; and 1 testicle germ cell teratoma.ConclusionEstimated malignancy frequency of 0.7% was reported during cSLE follow up in a multicentric series. Median disease activity and cumulative damage scores, by the time of malignancy diagnoses, were high; considering that reported in adult series.

A large cohort comparison of very late-onset systemic lupus erythematosus with younger-onset patients.

Age has a significant impact on systemic lupus erythematosus (SLE). However, data on very late-onset SLE (vlSLE) are scarce. We have compared the clinical and serological features of vlSLE patients with younger-onset patients. We assessed the clinical and laboratory data of all patients fulfilling SLE classification criteria evaluated at a university hospital from 1978 to 2023. Patients were divided into 4 groups according to age at diagnosis: juvenile SLE (jSLE <8 years); adult SLE (aSLE 18-49 years); late SLE (lSLE 50-59 years); vlSLE (≥60 years). 845 patients were enrolled. The jSLE, aSLE, lSLE, and vlSLE groups included 153, 630, 47, and 15 patients, respectively. The vlSLE group tended to have a lower female-to-male ratio (4:1; p=0.282), was mainly Caucasian (93.3%; p<0.001), and had the lowest survival time (20.3 years; p<0.001). vlSLE patients had the lowest prevalence of positive anti-dsDNA antibodies (26.7%; p=0.010) and low C3 levels (13.3%; p<0.001). Although arthritis was less common among vlSLE patients (73.3%; p=0.043), they more commonly developed Sjögren's syndrome (SS 33.3%; p<0.001) and rheumatoid arthritis (RA 13.3%; p<0.001). Infections and malignancy were the main causes of death. Compared with younger patients, in vlSLE, female predominance is less pronounced. Arthritis, anti-dsDNA antibodies and low C3 levels are less frequent. SS and RA are more common. Despite lower disease activity, vlSLE patients have the lowest survival rate. While uncommon, SLE should not be excluded as a possible diagnosis in the elderly.

Neuromodulation with aerobic exercise reduces fatigue in systemic lupus erythematosus: a randomised, sham-controlled, double-blind study.

Transcranial direct current stimulation (tDCS) combined with aerobic exercise (tDCS-AE) effectively reduces fatigue in patients with fibromyalgia. However, no study has assessed this method in systemic lupus erythematosus (SLE) patients with significant fatigue. Therefore, we evaluated the safety and efficacy of tDCS-AE for significant fatigue symptoms in adult female SLE patients. This randomised, sham-controlled, double-blind study included 25 patients with SLE in remission or low disease activity (SLEDAI-2K £4) and with significant fatigue [≥36 points on the Fatigue Severity Scale (FSS) or ≥38 points on the Modified Fatigue Scale (MFIS)]. The patients received sham or tDCS for five consecutive days. The anode and cathode were positioned at M1 and Fp2, respectively (international 10-20 EEG system). tDCS was applied at an intensity of 2mA, and density of 0.057mA/cm2 in the tDCS-AE group. Both groups underwent combined low-intensity treadmill exercise. FSS, MFIS, pain visual analogue scale, physical activity, and sleep quality were evaluated at baseline and on days 7, 30, and 60. Adherence and safety were assessed using a standardised questionnaire. Improvement in fatigue levels was observed in both groups. However, a sustained reduction in fatigue levels on days 30 and 60 occurred only with tDCS-AEs (p<0.05). No significant differences were observed in pain level, sleep quality, or physical activity. No disease flares occurred and the adverse effects were mild and transient. Finally, the patient's adherence to the treatment was satisfactory. Despite isolated AEs, there was an improvement in fatigue, however, only tDCS-AE maintained significant and sustained improvement.

FRI529 Hypothyroidism And Systemic Lupus Erythematosus: A Nationwide Analysis

Abstract Disclosure: F. Sami: None. S. Sami: None. A. Razok: None. T. Ayub: None. A. Olafimihan: None. Background: Hypothyroidism is the most common thyroid disease in Systemic Lupus Erythematosus (SLE) and more prevalent in SLE than the general population. Our aim is to study the prevalence, epidemiology and likelihood of hypothyroidism with SLE as well as impact on outcomes and healthcare burden. Methods: The National Inpatient Database from 2016-2019 was used to extract patient populations. Data was stratified to reflect national estimates. Adult patients with principal diagnosis of SLE and hypothyroidism as a primary or secondary diagnosis were identified. Epidemiology was compared. We analyzed mortality rates, hospital charges (THC) and length of stay (LOS). Secondary outcomes included sepsis, congestive heart failure (CHF), renal and respiratory failure, stroke and myocardial infarction (MI). Statistical analysis was performed with STATA17. Univariate and multivariate regression analyses adjusted for confounders. Results: Among 721,090 adult SLE patients, 17.64% had hypothyroidism. In SLE-hypothyroid group, there were more females (93.46% vs 87.35%, odds ratio 2.01) and whites ( 65.82%vs 33.53%, OR 2.37). The mean age was higher (59.95 SD 15.56 vs 50.91 SD 16.94, P-value 0.000) with significantly more patients in 60-80 years group (44.64% vs 28.56%) and less in 18-40 year age group (1.68% vs 29.01%). African-Americans and Hispanics were significantly less in hypothyroid group with OR 0.34 and 0.87 respectively. Charlson comorbidity Index was ssignificantly high (3.2 vs 2.97). Hypothyroidism was significantly more among higher socioeconomic class of SLE patients (20.62% vs 16.7%) and less prevalent among the low socioeconomic class (28.88% vs 35.36%) based on annual income. There was no significant rise in mortality when adjusted for confounders (1.93% vs 1.97%, P-value 0.702), mean length of stay (5.41 vs 5.46, P-value 0.284), or total hospital charges ($63372 vs 64065, P-value 0.273) between two groups. There was a significantly higher prevalence of MI (3.21% vs 2.9%, P-value 0.01,OR 1.11) and CHF (5.94% vs 5%, P-value 0.00,OR 1.2). Prevalence of sepsis (8.92% vs 8.77%, P-value 0.449), renal failure (37.94% vs 37.79%), respiratory failure (37.63% vs 37.84%) and stroke (0.88% vs 0.93%,) was comparable with no significant difference. Odds ratio for hypothyroidism in SLE was 1.5, p-value 0.000. Conclusion: SLE patients with hypothyroidism are more females, Caucasians, of higher mean age, between 60-80 years of age, and from higher socioeconomic status. There is no effect on mortality, LOS and THC, rate of sepsis, stroke, renal and respiratory failure with hypothyroidism. There is a significantly higher risk of MI and CHF. SLE patients have 1.5 times increased risk of developing hypothyroidism. This emphasizes screening at-risk individuals when suspicion arises, for timely diagnoses and improving outcomes. Presentation: Friday, June 16, 2023

Dosage optimization of tacrolimus based on the glucocorticoid dose and pharmacogenetics in adult patients with systemic lupus erythematosus

BackgroundThe purpose of the study was to develop a genotype-incorporated population pharmacokinetic (PPK) model of tacrolimus (TAC) in adults with systemic lupus erythematosus (SLE) to investigate the factors influencing TAC pharmacokinetics and to develop an individualized dosing regimen based on the model. In addition, a non-genotype-incorporated model was also established to assess its predictive performance compared to the genotype-incorporated model. MethodsA total of 365 trough concentrations from 133 adult SLE patients treated with TAC were collected to develop a genotype-incorporated PPK model and a non-genotype-incorporated PPK model of TAC using a nonlinear mixed-effects model (NONMEM). External validation of the two models was performed using data from an additional 29 patients. Goodness-of-fit diagnostic plots, bootstrap method, and normalized predictive distribution error test were used to validate the predictive performance and stability of the final models. The goodness-of-fit of the two final models was compared using the Akaike information criterion (AIC). The dosing regimen was optimized using Monte Carlo simulations based on the developed optimal model. ResultsThe typical value of the apparent clearance (CL/F) of TAC estimated in the final genotype-incorporated model was 14.3 L h−1 with inter-individual variability of 27.6%. CYP3A5 polymorphism and coadministered medication were significant factors affecting TAC-CL/F. CYP3A5 rs776746 GG genotype carriers had only 77.3% of the TAC-CL/F of AA or AG genotype carriers. Omeprazole reduced TAC-CL/F by 3.7 L h−1 when combined with TAC, while TAC-CL/F increased nonlinearly as glucocorticoid dose increased. Similar findings were demonstrated in the non-genotype-incorporated PPK model. Comparing these two models, the genotype-incorporated PPK model was superior to the non-genotype-incorporated PPK model (AIC = 643.19 vs. 657.425). Monte Carlo simulation based on the genotype-incorporated PPK model indicated that CYP3A5 rs776746 AA or AG genotype carriers required a 1/2–1 fold higher dose of TAC than GG genotype carriers to achieve the target concentration. And as the daily dose of prednisone increases, the dose of TAC required to reach the target concentration increases appropriately. ConclusionsWe developed the first pharmacogenetic-based PPK model of TAC in adult patients with SLE and proposed a dosing regimen based on glucocorticoid dose and CYP3A5 genotype according to the model, which could facilitate individualized dosing for TAC.

An Examination of Infection Incidence and Management in Systemic Lupus Erythematosus Patients: A Five-Year Review from a Saudi Arabian Center.

BACKGROUND Systemic lupus erythematosus (SLE) is a chronic autoimmune condition often associated with an increased susceptibility to infections. The infections in patients with SLE, primarily involving the skin, respiratory tract, and urinary tract, can significantly complicate disease management. This study aimed to evaluate the occurrence, management, and patient outcomes associated with infections in a group of 74 SLE patients at a single center in Saudi Arabia, spanning a 5-year period. MATERIAL AND METHODS An observational, retrospective study was conducted at the King Khalid University Hospital, Riyadh, Saudi Arabia. Patient medical records from January 2016 to December 2020 were examined. All adult SLE patients (age >14 years, as per hospital policy), confirmed by SLICC criteria, and admitted due to infections (determined by quick Sequential Organ Failure Assessment or qSOFA scores) were included in the study. RESULTS Of the 74 SLE patients studied, 79.7% were administered hydroxychloroquine. A majority (83.8%) were classified as low-risk for sepsis-associated mortality based on qSOFA scores (0-1), a fact noted by 41.9% of rheumatology fellows. The sputum cultures most frequently identified were Klebsiella pneumoniae, yeast, and Haemophilus influenzae (each accounting for 33.3% of cases). Furthermore, 4.1% of patients had extended-spectrum beta-lactamases infections, and 2.7% tested positive for COVID-19. A history of sepsis was more commonly observed among non-survivors (P=0.010). CONCLUSIONS The majority of patients were classified as low-risk for sepsis-associated mortality based on qSOFA scores, with two-thirds prescribed antibiotics within 1 h. The primary causes of death were multiorgan failure and cardiac arrest.

The Utility of Ultrasound in Evaluating Joint Pain in Systemic Lupus Erythematosus: Looking beyond Fibromyalgia.

Systemic lupus erythematosus (SLE) is a complex autoimmune condition with varied clinical presentations, and musculoskeletal pain is one of the most commonly associated symptoms. However, fibromyalgia (FM) is a prevalent co-existing condition in SLE patients that can also cause widespread pain, and in patients with both conditions, it is often difficult to distinguish the underlying cause of musculoskeletal pain and provide optimal therapy. A retrospective cohort study was conducted including all adult SLE patients who received musculoskeletal ultrasound (US) examinations for joint pain at the Ohio State University Wexner Medical Center between 1 July 2012, and 30 June 2022. Binary and multiple logistic regression analyses were performed to determine predictors of US-detected inflammatory arthritis as well as improved musculoskeletal pain. A total of 31 of 72 SLE patients (43.1%) had a co-existing diagnosis of FM. In binary logistic regression, a co-existing diagnosis of FM was not significantly associated with US-detected inflammatory arthritis. In multiple logistic regression analysis, clinically detected synovitis was significantly associated with US-detected inflammatory arthritis (aOR, 142.35, p < 0.01), and there was also a weak association with erythrocyte sedimentation rate (ESR) (aOR 1.04, p = 0.05). In separate multiple logistic regression analysis, US-guided intra-articular steroid injection was the only predictor of improved joint pain at follow-up visit (aOR 18.43, p < 0.001). Musculoskeletal US can be an effective modality to detect inflammatory arthritis as well as to guide targeted intra-articular steroid injection to alleviate joint pain in SLE patients with or without FM.