Unraveling the diagnostic odyssey: stimulator of interferon gene-associated vasculopathy with onset in infancy in a 30-year-old female.

Stimulator of interferon gene (STING)-associated vasculopathy with onset in infancy (SAVI) is an extremely rare autoinflammatory disease. We present the case of a female Korean patient with early-onset interstitial lung disease who was initially suspected to have systemic lupus erythematosus (SLE) but was ultimately diagnosed with SAVI. The patient exhibited signs of interstitial lung disease and cutaneous manifestations before the age of 1 year and continued to have recurrent fever accompanied by pulmonary infiltrates. Based on positive findings for antibodies associated with SLE, such as antinuclear antibodies and anti-double-stranded DNA, the pulmonary involvement was considered a manifestation of SLE. Another significant symptom was recurrent skin ulceration, which led to partial spontaneous amputation of most of the toes due to inflammation. Given the early onset of interstitial lung disease, severe skin ulcers, and symptoms resembling SLE, autoinflammatory syndrome, especially SAVI was suspected. Following confirmation by genetic testing at age 29 years, the patient was started on tofacitinib, a Janus kinase inhibitor. Despite the prolonged use of multiple immunosuppressive therapies, the patient's lung condition continued to worsen, ultimately requiring lung transplantation. This observational report highlights the importance of considering SAVI as a potential diagnosis when manifestations of interstitial lung disease are observed during infancy. Early proactive treatment is crucial for lung involvement, as this can have long-term effects on patient's prognosis.

Clinical characteristics and prognostic value of autoantibody profile in children with monogenic lupus.

Objective: To report the frequency of selected autoantibodies and their associations with clinical features in Arab children with monogenic lupus. Methods: This study was retrospective single-center study of genetically confirmed monogenic lupus cases at childhood lupus clinic at King Faisal Specialist Hospital and Research Center, from June 1997 to July 2022. We excluded familial lupus without genetic testing and patients with insufficient data. Collected data comprised clinical and laboratory findings, including the autoantibody profile, which included the anti-double-stranded DNA (anti-dsDNA), anti-Smith, anti-Sjögren's-syndrome-related antigen A (anti-SSA), anti-Sjögren's-syndrome-related antigen B (anti-SSB), and antiphospholipid (APL) antibodies. Also, disease activity and accrual disease damage were collected at the last follow-up visit. Results: This study enrolled 27 Arab patients (14 males) with a median age of 11 years (interquartile range 8.0~16 years), with 63% having early-onset disease. The consanguinity rate and family history of lupus were high (74.1% and 55.6%, respectively). The most frequent clinical features were hematological (96.3%), fever (81.5%), mucocutaneous lesions (85.2%), and renal (66.7%). The frequency of the APL antibodies was 59.3%, anti-dsDNA was 55.6%, and anti-Smith and anti-SSA were 48.2% and 44.4%, respectively. Moreover, dsDNA antibodies were significantly associated with musculoskeletal complaints (p<0.05). Likewise, both anti-Smith and anti-SSA antibodies were linked to failure to thrive and recurrent infections in the univariate analysis (p<0.05). Conclusion: Our study reveals autoantibody frequencies and their association with clinical and prognostic in a substantial monogenic lupus cohort. Distinct clinical manifestations and prognosis association with certain autoantibodies support the idea that monogenic lupus is a distinctive form of lupus. Larger studies needed to validate these findings.

Monoclonal antibodies targeting interleukins for systemic lupus erythematosus: updates in early clinical drug development.

INTRODUCTION: the advent of biological therapies has already revolutionized treatment strategies and disease course of several rheumatologic conditions, and monoclonal antibodies (mAbs) targeting cytokines and interleukins represent a considerable portion of this family of drugs. In Systemic Lupus Erythematosus (SLE) dysregulation of different cytokine and interleukin-related pathways have been linked to disease development and perpetration, offering palatable therapeutic targets addressable via such mAbs. AREAS COVERED: In this review, we provide an overview of the different biological therapies under development targeting cytokines and interleukins, with a focus on mAbs, while providing the rationale behind their choice as therapeutic targets and analyzing the scientific evidence linking them to SLE pathogenesis. EXPERT OPINION: an unprecedented number of clinical trials on biological drugs targeting different immunological pathways are ongoing in SLE. Their success might allow us to tackle present challenges of SLE management, including the overuse of glucocorticoids in daily clinical practice, as well as SLE heterogenicity in treatment response among different individuals, hopefully paving the way toward precision medicine.

Predictability of the Delta Neutrophil Index and Other Blood Parameters on Perinatal Outcomes in Pregnant Women With Systemic Lupus Erythematosus.

PROBLEM: This study aimed to evaluate the predictive value of delta neutrophil index (DNI), a peripheral blood parameter, on perinatal outcomes in pregnant women with systemic lupus erythematosus (SLE). METHOD OF STUDY: One hundred eighty-one participants, 78 pregnant women with SLE, and 103 healthy pregnant women were included in this retrospective study. Peripheral blood parameters including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and DNI taken in the first trimester were compared between groups. RESULTS: NLR, PLR, and DNI were significantly higher in the SLE group (p = 0.027, p = 0.007, p = 0.0001, respectively). The same parameters were not found to be significant in determining disease activity in pregnant women with SLE (p > 0.05). When the predictive value of DNI for SGA in pregnancies with SLE was evaluated by receiver operating characteristic curve (ROC), the area under the ROC curve (AUC) was 0.666 (95% CI; 0.544-0.788, p = 0.018) with 84.6% sensitivity, 53.8% specificity, 56.0% PPV, and 78.1% NPV at a cut-off value of 0.16. The predictive value of DNI according to ROC for stillbirth in pregnancies with SLE was AUC 0.731 (95% CI: 0.539-0.923, p = 0.019) with a cut-off value of 0.17, sensitivity of 90%, specificity of 51.5%, PPV of 58.5%, and NPV of 87.2%. CONCLUSIONS: Although DNI's prediction of SGA and stillbirth in pregnant women with SLE is encouraging, it needs more evidence from prospective studies with larger series.

Is systemic lupus erythematosus linked to Immunoglobulin G4 Autoantibodies?

Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder characterized by a hyperactive immune system with multiple abnormalities in B-cell proliferation, antibody production, T-cell regulation, and immune complex (IC) formation. In humans, Immunoglobulin (Ig) G is found in four subclasses. IgG1-IgG4, which are distinguished by both structural and biological differences. Fab-arm Exchange (FAE), specific biases in the IgG4 response repertoire, and a decreased capacity to induce effector functions mediated by interactions in the fragment crystallizable (Fc) region are just a few of the distinctive characteristics of IgG4. The recent finding of the presence of double-stranded DNA (dsDNA) and antinuclear antibody (ANA)-IgG4 has raised attention to this IgG subclass and its possible role in SLE. IgG4 was previously believed to just have anti-inflammatory effects by inhibiting immune responses, but recent studies have shown that these antibodies can also play a role in the onset and development of some clinical disorders. To consider the clinical effects of IgG4 presence, it is necessary to discuss its characteristics, which could underlie the potential role it can play in SLE. Therefore, this study aimed to comprehensively review the role of IgG4 in SLE to elucidate the collective incidence of high IgG4 levels reported in some SLE patients.

Comparison of the Quantitative Values of Peripapillary, Macular and Choriocapillary Microvascular Structures According to the Presence of Lupus Nephritis in Patients with Systemic Lupus Erythematosus.

PURPOSE: To determine whether there are quantitative changes in macular, choriocapillary, and peripapillary microvascular structures using optical coherence tomography angiography (OCTA) due to the presence of lupus nephritis (LN) in patients with systemic lupus erythematosus (SLE) and to investigate the correlation between these quantitative values and disease duration. METHODS: Fifty -five patients followed up in the rheumatology clinic with an SLE diagnosis were evaluated. As the control group, 61 eyes of 61 age- and gender-matched healthy individuals were included. The patients with SLE were further divided into two groups: those with LN (29 eyes) and those without LN (26 eyes). Macular, choriocapillary, and peripapillary microvascular structures were quantitatively analyzed with OCTA and compared between the three study groups. A correlation analysis of the measured quantitative values and disease duration was also performed. RESULTS: In macular microvascular (MMV) analysis, the vessel densities (VDs) of the superficial capillary plexus (SCP) decreased in both SLE groups, while those of the deep capillary plexus (DCP) decreased only in the SLE group with LN. The foveal density significantly decreased in the SLE group with LN compared to the control group, there were no significant differences in terms of the radial peripapillary capillary VDs or the choriocapillaris flow area. Disease duration was not correlated with any of the quantitative parameters measured by OCTA in either SLE group. CONCLUSIONS: Identifying differences in retinal microvascular circulation in SLE patients with kidney damage helps predict possible nephropathy and therefore guides the treatment process of this patient.

Intercurrent infection as a risk factor for disease flares in patients with systemic lupus erythematosus.

OBJECTIVE: To determine whether intercurrent infections are a risk factor for subsequent disease flares in systemic lupus erythematosus (SLE). METHODS: Demographic and clinical characteristics of 203 patients with SLE participating in the Amsterdam SLE cohort were collected at baseline and during follow-up. Collection of data on infections and SLE flares was registry-based and infections and flares were categorised as minor or major, based on predefined criteria. Proportional hazard models with recurrent events and time-varying covariates were used to estimate the HR of SLE flares. RESULTS: The incidence rates of major and minor infections were 5.3 per 100 patient years and 63.9 per 100 patient years, respectively. The incidence rates of flares were 3.6 and 15.1 per 100 patient years for major flares and minor flares, respectively.In the proportional hazard model, intercurrent infections (major and minor combined) were associated with the occurrence of SLE flares (major and minor combined; HR 1.9, 95% CI: 1.3 to 2.9). The hazard ratio for a major SLE flare following a major infection was 7.4 (95% CI: 2.2 to 24.6). Major infections were not associated with the occurrence of minor flares. CONCLUSIONS: The results of the present study show that intercurrent infections are associated with subsequent SLE flares, which supports the hypothesis that infections may trigger SLE flares.

Unilateral Alveolar Hemorrhage: A Rare Pulmonary Complication in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease that presents a broad spectrum of clinical manifestations. Alveolar hemorrhage in SLE is rare and has a poor prognosis. We present the case of a patient with a diagnosis of SLE and lupus nephropathy on hemodialysis who presented criteria for alveolar hemorrhage with unilateral involvement, with clinical improvement after the administration of steroid boluses. The uncommon presentation of unilateral pulmonary involvement and the importance of making an adequate protocol for ruling out differential diagnoses are highlighted.

Challenges and opportunities in access to care for systemic lupus erythematosus patients across Europe and worldwide.

SLE presents significant challenges for patients and health-care professionals (HCPs), both across Europe and worldwide. Improving health-care outcomes for patients with SLE requires a comprehensive understanding of patient disease pathways. In particular, the geographical distance between SLE patients and specialized care centres, combined with the scarcity of rheumatologists, exacerbates delays in diagnosis and management. Also, the initial SLE symptoms can often be non-specific, and providing guidelines for primary HCPs and other non-specialists is extremely important. Improvement in access to treatment is also important, with several recently approved therapies for SLE not being available in several European countries and many low- and middle-income countries (LMICs). Furthermore, in the LMICs in which these treatments are available, they are not always covered by the health-care system, making their access almost impossible for those of lower socio-economic status. A number of provisions are already in place within the European Union, to improve access to care for patients with rare and complex diseases, including those with SLE. In particular, European Reference Networks (ERNs), such the ERN for Autoimmune Diseases ReCONNET, are virtual networks involving HCPs across Europe with the aim of improving the care of patients with rare and complex diseases that require highly specialized treatment and a concentration of knowledge and resources. In addition, lupus patient organizations such as Lupus Europe play a crucial role in raising awareness of SLE and advocating for improved access to care. Together, we can work towards a future where all people living with lupus receive the comprehensive and timely care they deserve.

Plasma proteins and inflammatory dermatoses: proteome-wide Mendelian randomization and colocalization analyses.

Current genome-wide association studies (GWAS) of plasma proteomes provide additional possibilities for finding new drug targets for inflammatory dermatoses. We performed proteome-wide Mendelian randomization (MR) and colocalization analyses to identify novel potential drug targets for inflammatory dermatoses. We performed MR and colocalization analysis using genetic variation as instrumental variables to determine the causal relationship between circulating plasma proteins and inflammatory dermatoses. 5 plasma proteins were found to be causally associated with dermatitis eczematosa, SLE, urticaria and psoriasis using cis-pQTLs as instrumental variables, but not found in AD and LP. 19 candidate genes with high colocalization evidence were identified. These potential drug targets still require more research and rigorous validation in future trials.

Unilateral Pleural Effusion as an Initial Manifestation of Systemic Lupus Erythematosus in a Patient of Advanced Age.

Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disease that can manifest in older individuals, presenting unique diagnostic challenges because of its atypical presentations and comorbidities. Pleural effusion is a relatively uncommon manifestation of SLE, with studies suggesting a higher prevalence in older than younger patients. We herein report an atypical case of delayed-onset SLE in a 75-year-old man with left-sided pleural effusion as the initial presentation. This case underscores the difficulty of diagnosing SLE in patients of advanced age and the importance of considering a broad range of differential diagnoses, even in cases that may suggest a more common disease. This case also highlights the fact that unilateral pleural effusion can be an initial manifestation of SLE, and when the cause of the pleural effusion is unclear, SLE should be considered as a potential diagnosis.

Frequency and predictors for early-achieved lupus low disease activity state in systemic lupus erythematosus patients treated with telitacicept or belimumab: A real-life, single-center observational study.

Objective: To collect real-world data regarding the attainment of the early-achieved lupus low disease activity state (LLDAS) in systemic lupus erythematosus (SLE) patients receiving telitacicept or belimumab treatment, and identify factors predictive of target achievement. Methods: Eighty-seven SLE patients who received telitacicept (N=42) or belimumab (N=45) were retrospectively reviewed in this observational study. Clinical and laboratory data, disease activity assessment, and glucocorticoid dosage were collected for analysis. Achieving LLDAS at least once within 24 weeks post-treatment was considered as early-achieved LLDAS. Multivariate regression was used to assess baseline predictive variables for early-achieved LLDAS. Subgroup analysis and interaction tests were also performed to examine the robustness of the results across different sets of baseline characteristics. Prognostic stratification for early-achieved LLDAS was established based on the identified risk factors. Results: During the 24-week follow-up period, LLDAS was achieved by at least one time in 49.43% (43/87) of the patients, with sustained achievement through week 24 observed in 36 out of these 43 patients (83.27%). Multivariate analysis revealed that early achievement of LLDAS was particularly observed in patients with higher baseline lymphocyte counts [HR=1.79, 95% CI (1.19-2.67), P=0.005]and serum albumin levels [HR=1.06, 95% CI (1.003-1.12), P=0.039]. Conversely, hematological involvement [HR=0.48, 95% CI (0.24-0.93), P=0.031] predicted lower attainment of early-achieved LLDAS. The use of telitacicept was associated with a reduced risk of failing to attain early achievement of LLDAS [HR=2.55, 95% CI (1.36-4.79), P=0.004]. Subgroup analyses and interaction tests showed a stable relationship between the telitacicept use and LLDAS achievement. The results remained consistent across all subgroup analyses. Significant differences (P<0.001) were observed in the Kaplan-Meier estimates for LLDAS among risk groups based on the number of identified risk factors. Conclusion: The achievement of LLDAS is attainable in the management of SLE patients undergoing treatment with telitacicept or belimumab in real-life clinical practice. Baseline lymphocyte counts, serum albumin levels, hematological involvement and the use of telitacicept serve as robust predictors for early-achieved LLDAS, helping to identify patients who are likely to benefit on the treatment.

Severe Hypertrophic Cardiomyopathy Associated With Hydroxychloroquine in a Young Woman With Systemic Lupus Erythematosus: A Case Report and Review of the Literature.

The use of the antimalarial drug hydroxychloroquine is a standard treatment in patients with systemic lupus erythematosus. It helps reduce disease-associated damage, prevents disease flare, and improves overall survival. The mechanism of action of hydroxychloroquine includes interference with lysosomal degradation of cells leading to the accumulation of vacuoles. Retinopathy is a well-described adverse effect of hydroxychloroquine, thus requiring screening with an ophthalmologist after prolonged use. Although rarely reported, cardiac adverse effects of hydroxychloroquine can also occur. In this report, we present a case of a 23-year-old woman with systemic lupus erythematosus on hydroxychloroquine who presented with stroke possibly due to Libman-Sacks endocarditis and was found to have severe hypertrophic cardiomyopathy on transthoracic echocardiogram.

Investigating the therapeutic mechanism of Jiedu-Quyu-Ziyin Fang on systemic lupus erythematosus through the ERα-miRNA-TLR7 immune axis.

Jiedu-Quyu-Ziyin Fang (JQZF) is a formula that has been empirically used for the treatment of SLE in clinical practice. JQZF has become an approved hospital prescription in China. Fifteen MRL/lpr mice were randomly divided into three groups: Model, JQZF, and JQZF + GC, with five mice in each group. Five MRL/MPJ mice were used as the Blank group. After 8 weeks of administration, peripheral blood serum was collected to detect anti-dsDNA antibodies and complement C3 levels. Spleen B cells were collected to detect the expression of TLR7 and NF-κBp65 mRNA, and correlation analysis was performed. Transcriptome sequencing analysis was also performed on spleen B cells. Further, key miRNA and key gene mRNA expression were detected by RT-qPCR, and key protein expression levels were detected by Western blot method. Bioinformatics methods predicted that ESR1 is a key target of JQZF action on SLE, hsa-miR-146a-5p is one of the key miRNAs, and KEGG pathway analysis showed that NF-κB signaling pathway is its key signaling pathway. Transcriptome sequencing of MRL/lpr mouse spleen B cells revealed that the differential genes between the JQZF and Model groups were enriched in Toll-like receptor signaling pathway, NF-κB signaling pathway, Estrogen signaling pathway, etc. Animal studies show that JQZF treatment significantly boosts serum C3 and lowers anti-dsDNA antibodies (P < 0.01). On the molecular level, JQZF suppresses TLR7 and NF-κBp65 mRNA in spleen B cells, with TLR7 mRNA positively linked to anti-dsDNA titers and negatively to serum C3. Further cellular work demonstrates that JQZF reverses the increased IRAK1 and TRAF6 expression seen after miR146a inhibition. Additionally, post-ERα inhibition, JQZF continues to upregulate miR146a and more significantly reduces TLR7 mRNA expression (P < 0.01), pointing to ERα's pivotal role in the miR146a-TLR7 axis. These results indicate JQZF alleviates SLE by adjusting the ERα-miR146a-TLR7 loop, showcasing its mechanism and therapeutic potential for SLE.

Ovarian function in patients with systemic lupus erythematosus: Pathogenesis, drug application and prospective therapies.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease in which multiple organs are damaged that prevails in fertile women. Currently, glucocorticoids and immunosuppressants are widely used to treat SLE patients. However, ovarian dysfunction occurs following the use of these drugs in women with SLE. Here, we summarize recent progress in terms of understanding ovarian injury, the effects of drug application and strategies to improve ovarian function in women with SLE. This review could be helpful to precisely cure SLE in women desiring to have offspring.

Coexistence of multiple sclerosis and systemic lupus erythematosus - a case report.

Purpose: Multiple sclerosis (MS) and systemic lupus erythematosus (SLE) are two autoimmune diseases that are relatively common, especially in women. However, it is extremely rare for them to coexist in a single patient (only 18 cases have been recorded worldwide). Both affect the nervous system and may manifest in identical ways. This creates significant difficulties, both in terms of diagnosis and choice of appropriate therapy. Case description: A 54-year-old female patient with quadriparesis, superficial sensory disturbance and gait and balance disorders was diagnosed with primary progressive MS according to McDonald's criteria. The magnetic resonance images were typical for MS. Previously, in 2013, she was diagnosed with SLE, treated successfully, and is currently in remission. After excluding neuropsychiatric lupus, ocrelizumab treatment was administered, with good clinical results. Comment: Adequate differentiation (magnetic resonance imaging, analysis of cerebrospinal fluid, clinical observation) as to whether the patient's symptoms are related to MS or to SLE nervous system involvement is the basis for proper diagnosis and treatment.

Disseminated Hypertrophic Discoid Lupus Erythematosus in a Patient with Vitiligo: A Case Report and Literature Review.

Vitiligo has been reported to occur in association with lupus erythematosus (LE) and other autoimmune diseases. However, it remains unclear whether this association occurs because of shared immunopathogenesis. We hereby describe a case of discoid lupus erythematosus (DLE) in a 51-year-old man with a 3 years history of skin lesions on his face, arms, and the V zone of the neck, and with the coexistence of vitiligo for 12 years, who developed from DLE to hypertrophic discoid lupus erythematosus (HDLE) after 10 months. We reviewed the previously reported cases to summarize the clinical characteristics of these patients and hope it may provide a reference for dermatologists.

Kidney transplantation from a systemic lupus erythematosus donor and 1-year follow-up: A case report.

Systemic lupus erythematosus (SLE) is usually regarded as a relative contraindication for deceased kidney donation. The pathological variations because of the changes in the immune environment after kidney transplantation (KT) are unclear, and the recovery of renal function is poorly understood. We present a case of KT from a deceased donor with SLE who was followed-up for one year. Although SLE-related hemangioma developed during the perioperative period, it was cured after interventional treatment. A pre-planned biopsy was performed one year after KT, and it was found that most of the pathological changes and immunofluorescent markers of lupus had resolved. Renal function was stable, and urinary protein and occult blood levels reduced one year after KT.

Referrals for rheumatologic evaluation following a positive antinuclear antibody test result. A cross-sectional single center Brazilian study.

BACKGROUND: In general, patients are referred for rheumatological evaluation due to isolated laboratory abnormalities, especially antinuclear antibody (ANA) positivity, with the risk of more severe patients remaining on the waiting list for longer than desired. The aim of this study was to analyze the demographic, clinical, and laboratory information of patients referred to a specialized rheumatological care unit because of positive antinuclear antibody. METHODS: This is a retrospective study of 99 out of 1670 patients seen by the same rheumatologist between 01/01/2011 and 01/01/2019. Patients whose referrals were exclusively due to the ANA test result and the specialist's final diagnosis being "abnormal finding of serum immunological test" (ICD-10 R769) were included. Sociodemographic, clinical, and laboratory information were extracted from the consulting rheumatologist's chart. Descriptive statistics were used for data analysis. RESULTS: A total of 99 patients were included, most of whom were female (84.8%) with a median age of 49 years. At the moment of specialist's appointment, 97 patients (97.9%) repeated the ANA test, and 77 patients remained positive. Of these, only 35 (35.35%) were in a high titer range (greater than or equal to 1:320). Complete blood count for cytopenia's investigation was not performed in a high percentage of patients (22.2%), as well as urinalysis (31.3%). In addition, more than 70% of patients score 0 to 1 classification criteria for Systemic Lupus Erythematosus, according to SLE - ACR 1987 (American College of Rheumatology) and SLICC 2012 (Systemic Lupus International Collaborating Clinics). CONCLUSIONS: Most patients are still referred for specialized evaluation due to the misinterpretation of laboratory tests that were inappropriately requested in patients without clinical evidence of autoimmune rheumatic disease.