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Because Systemic Lupus Erythematosus (SLE) is a rare disease, and due to the significant prognostic impact of early management, a diagnosis confirmed by a physician with experience in SLE is recommended, for example from an expert center. Once the diagnosis is confirmed, existing manifestations should be identified in particular, renal involvement by an assessment of proteinuria, disease activity and severity should be determined, potential complications anticipated, associated diseases searched for, and the patient's socioprofessional and family context noted. Therapeutic management of SLE includes patient education on recognizing symptoms, understanding disease progression as well as when they should seek medical advice. Patients are informed about routine checkups, treatment side effects, and the need for regular vaccinations, especially if they are receiving immunosuppressive treatment. They are also advised on lifestyle factors such as the risks of smoking, sun exposure, and dietary adjustments, especially when they are receiving corticosteroids. The importance of contraception, particularly when teratogenic medications are being used, and regular cancer screening are emphasized. Support networks can help relieve a patient's isolation. The first-line medical treatment of SLE is hydroxychloroquine (HCQ), possibly combined with an immunosuppressant and/or low-dose corticosteroid therapy. The treatment of flares depends on their severity, and typically involves HCQ and NSAIDs, but may be escalated to corticosteroid therapy with immunosuppressants or biologic therapies in moderate to severe cases. Because there is no curative treatment, the goals of therapy are patient comfort, preventing progression and flares, and preserving overall long-term health and fertility. The frequency of follow-up visits depends on disease severity and any new symptoms. Regular specialized assessments are necessary, especially when treatment changes, but a frequency of every 3 to 6 months is recommended during periods of remission and monthly during active or severe disease, especially in children. These assessments include both clinical and laboratory tests to monitor complications and disease activity, with specific attention to proteinuria. [ABSTRACT FROM AUTHOR]

Introduction/Objectives: The heterodimer exostosin-1/exostosin-2 (EXO-1/2) is a novel antigen observed in membranous nephropathy associated with systemic lupus erythematosus. This study aimed to evaluate the association between EXO-1/2 positivity in kidney biopsy and kidney outcomes. Methods: The kidney biopsy tissue from 50 class 5 lupus nephritis (LN) and 55 mixed class 3/4 + 5 LN patients was stained for EXO-1/2. Baseline clinical and histological characteristics were compared between EXO-1/2 positive and EXO-1/2 negative patients. Time-to-event analyses were performed to compare rates of response to therapy, kidney flares, and progression to a 40% decline of the glomerular filtration rate (eGFR), doubling of serum creatinine, and kidney failure. Results: Fourteen out of 50 (28%) of class 5 and 5 out of 55 (9%) of mixed class 3/4 + 5 LN stained positive for EXO-1/2. Patients with class 5 LN and EXO-1/2 positive stain were younger, with better kidney function at presentation, and lower scarring in the kidney biopsy analysis. Over a median follow-up of 100 months, patients with positive EXO-1/2 staining had significantly lower rates of progression in the full cohort. When analyzed separately in class 5 and mixed class LN subgroups, there were significantly lower rates of progression to a 40% decline of the eGFR and non-statistically significant trends for doubling of serum creatinine and kidney failure. Conclusion: EXO-1/2 is a novel antigen detected in class 5 LN and associated with a good prognosis of kidney function. The incorporation of EXO-1/2 staining in clinical practice can potentially modify the management of LN due to its prognostic implications. Key Points • Exostosin-1/exostosin-2 antigen has been found in cases of membranous nephropathy associated with autoimmune diseases such as systemic lupus erythematosus. • Exostosin-1/exostosin-2 staining in the kidney biopsy of class 5 or mixed class 3/4 + 5 lupus nephritis is associated with a good long-term prognosis of kidney function. • The incorporation of exostosin-1/exostosin-2 staining into clinical practice can potentially modify management due to its prognostic implications. [ABSTRACT FROM AUTHOR]

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

Introduction: T follicular (TFH) and peripheral helper (TPH) cells have been increasingly recognized as a pathogenic subset of CD4 T cells in systemic lupus erythematosus (SLE). The SLAM Associated Protein (SAP) regulates TFH and TPH function by binding to the co-stimulatory signaling lymphocyte activation molecule family (SLAMF) receptors that mediate T cell - B cell interactions. SAP and SLAMF are critical for TPH-dependent B cell maturation into autoantibodyproducing plasma cells that characterize SLE pathogenesis. We hypothesized that SAP-expressing TPH cells are involved in the pathogenesis of lupus nephritis (LN). Methods: Peripheral blood mononuclear cells (PBMC) were isolated using density gradient separation from whole blood. Cells were stained for cell surface markers, followed by permeabilization and staining of intracellular SAP for spectral flow cytometry analysis. We also analyzed SAP expression from renal infiltrating LN T cells using the available single-cell RNA sequencing (scRNA seq) Accelerated Medicines Partnership (AMP) SLE dataset. Results: PBMC from 30 patients with SLE (34 ± 10 years old, 83% female), including 10 patients with LN, were analyzed. We found an increase in total SAPpositive CD4 and CD8 T cells in SLE compared with controls (55.5 ± 2.6 vs. 41.3 ± 3.4, p=0.007, and 52.5 ± 3.0 vs. 39.2 ± 2.8, p=0.007 respectively). In CD4 T cells, the highest SAP expression was in the TPH subset. The frequency of SAP+TPH in circulation correlated with disease activity; SLE patients with renal disease had higher levels of circulating SAP+TPH that remained significant after adjusting for age, sex, race, low complements, and elevated anti-dsDNA (p=0.014). scRNAseq data of renal infiltrating T cells in LN identified SAP expression to localize to the TFH-like CD4 cluster and GZMK+ CD8 cluster. Increased SAP expression in LN was associated with the differential expression of SLAMF3 and SLAMF7 and granzyme K and EOMES. The existence of two predominant SAP-expressing subsets, the TFH-like CD4 T cells, and GZMK+ effector CD8 T cells, was verified using scRNA-seq data from a human transcriptomic atlas of fifteen major organs. Conclusion: The expansion of SAP-expressing T helper cells was associated with LN in our cohort and verified using scRNA-seq data of renal infiltrating T cells. Improved SLAM and SAP signaling understanding can identify new therapeutic targets in LN. [ABSTRACT FROM AUTHOR]

Hematopoietic stem cell transplantation (HSCT) for severe ADs was developed over the past 25 years and is now validated by national and international medical societies for severe early systemic sclerosis (SSc) and relapsing-remitting multiple sclerosis (MS) and available as part of routine care in accredited center. HSCT is also recommended, with varying levels of evidence, as an alternative treatment for several ADs, when refractory to conventional therapy, including specific cases of connective tissue diseases or vasculitis, inflammatory neurological diseases, and more rarely severe refractory Crohn's disease. The aim of this document was to provide guidelines for the current indications, procedures and follow-up of HSCT in ADs. Patient safety considerations are central to guidance on patient selection and conditioning, always validated at the national MATHEC multidisciplinary team meeting (MDTM) based on recent (less than 3 months) thorough patient evaluation. HSCT procedural aspects and follow-up are then carried out within appropriately experienced and Joint Accreditation Committee of International Society for Cellular Therapy and SFGM-TC accredited centres in close collaboration with the ADs specialist. These French recommendations were performed according to HAS/FAI2R standard operating procedures and coordinated by the Île-de-France MATHEC Reference Centre for Rare Systemic Autoimmune Diseases (CRMR MATHEC) within the Filière FAI2R and in association with the Filière MaRIH. The task force consisted of 3 patients and 64 clinical experts from various specialties and French centres. These data-derived and consensus-derived recommendations will help clinicians to propose HSCT for their severe ADs patients in an evidence-based way. These recommendations also give directions for future clinical research in this area. These recommendations will be updated according to newly emerging data. Of note, other cell therapies that have not yet been approved for clinical practice or are the subject of ongoing clinical research will not be addressed in this document. [ABSTRACT FROM AUTHOR]

Raynaud's phenomenon (RP) is a relatively common disease with both primary and secondary forms. It is well understood as a vasospastic condition affecting the acral and digital arteries, resulting in characteristic, well-demarcated color changes typically in the hands and feet in response to cold or stress. Secondary RP (SRP) has been described in association with a variety of rheumatologic and nonrheumatologic diseases, environmental exposures, and/or medications. While both primary RP and SRP may impact the quality of life, SRP may lead to permanent and potentially devastating tissue destruction when undiagnosed and untreated. It is therefore crucial for dermatologists to distinguish between primary and secondary disease forms early in clinical evaluation, investigate potential underlying causes, and risk stratify SRP patients for the development of associated autoimmune connective tissue disease. The epidemiology, pathogenesis, and clinical presentation and diagnosis of both forms of RP are described in detail in this review article. [ABSTRACT FROM AUTHOR]

Raynaud phenomenon (RP) presents with either primary or secondary disease, and both have the potential to negatively impact patient quality of life. First-line management of RP should include lifestyle modifications in all patients. Some patients with primary RP and most with secondary RP require pharmacologic therapies, which may include calcium channel blockers, topical nitrates, phosphodiesterase 5 inhibitors, or endothelin antagonists. Additional approaches to treatment for those with signs of critical ischemia or those who fail pharmacologic therapy include botulinum toxin injection and digital sympathectomy. Herein, we describe in detail the treatment options for patients with RP as well as provide treatment algorithms for each RP subtype. [ABSTRACT FROM AUTHOR]

Le dosage de l'hydroxychloroquine (HCQ) peut être effectué facilement par chromatographie liquide de haute performance à partir d'un prélèvement sanguin. Les premières études sur son intérêt remontent aux années 1990 dans la polyarthrite rhumatoïde (PR). Il est alors observé une variabilité interindividuelle des concentrations sanguines de l'HCQ, avec une corrélation entre concentration sanguine, efficacité et tolérance. Au début des années 2000, des recherches sur l'intérêt de ce dosage ont montré que des concentrations sanguines basses étaient associées, à l'instar de la PR, à l'activité clinique du lupus systémique. L'essai PLUS a étudié l'intérêt d'augmenter les doses prescrites d'HCQ chez les patients avec une concentration sanguine basse, mais n'a pas montré que cette augmentation permettait une réduction des poussées. Plus intéressant, la seule information auprès du patient d'une concentration sanguine insuffisante de l'HCQ semblait permettre une autocorrection par celui-ci, suggérant surtout un problème d'adhésion au traitement, plus que de dose prescrite. Des études ultérieures ont renforcé cette observation, liant des taux bas d'HCQ à une mauvaise adhésion thérapeutique et à un risque de développement de séquelles de la maladie. Cette non-adhérence est multifactorielle : crainte des effets secondaires de l'HCQ, impression d'inutilité de ce traitement, ou non-acceptation de la maladie. L'HCQ expose à de rares effets secondaires, notamment une rétinopathie, complication la plus redoutée. Une surveillance ophtalmologique est recommandée, mais l'utilisation du dosage sanguin pourrait aider à déterminer la « juste » dose pour chaque patient. Le dosage sanguin de l'HCQ est donc un atout supplémentaire pour un meilleur suivi des patients, permettant d'évaluer l'adhérence au traitement, d'éviter d'inutiles escalades thérapeutiques et de prévenir des surdosages pourvoyeurs de complications. Hydroxychloroquine (HCQ) blood level can be easily measured through high-performance liquid chromatography from a blood sample. The earliest studies on its significance date back to the 1990s for rheumatoid arthritis (RA). At that time, an interindividual variability in blood concentrations of HCQ was observed, with a correlation between blood concentration, efficacy, and tolerance. In the early 2000s, research on the value of this dosing showed that low blood concentrations were associated, as with RA, with the clinical activity of systemic lupus. The PLUS trial investigated the benefit of increasing prescribed doses of HCQ in patients with low blood concentration but did not show that this increase led to a reduction in flare-ups. Interestingly, merely informing the patient of an insufficient blood concentration of HCQ seemed to allow self-correction by the patient, suggesting primarily an adherence issue to the treatment rather than the prescribed dose. Subsequent studies reinforced this observation, linking low HCQ levels to poor therapeutic adherence and a risk of developing disease damages. This non-adherence is multifactorial: fear of HCQ side effects, the impression of the treatment's futility, or non-acceptance of the disease. HCQ has rare side effects, notably retinopathy, the most dreaded complication. Ophthalmological monitoring is recommended, but the use of blood dosing could help determine the "right" dose for each patient. Blood dosing of HCQ is, therefore, an added asset for better patient monitoring, allowing for the evaluation of treatment adherence, avoiding unnecessary therapeutic escalations, and preventing overdoses leading to complications. [ABSTRACT FROM AUTHOR]

L'hydroxychloroquine (HCQ) a été récemment sous les feux de la rampe en raison de son utilisation dans le traitement de la COVID-19, ce qui a suscité des inquiétudes concernant sa tolérance cardiaque. Toutefois, l'efficacité de l'HCQ dans les maladies auto-immunes, notamment dans le lupus systémique, est bien établie. Elle offre une amélioration significative des symptômes et une prévention des lésions tissulaires. Pour prévenir des effets secondaires rares mais potentiellement graves, il est essentiel de surveiller les patients et de prendre en compte les rares contre-indications. La rétinopathie reste la complication la plus redoutée au très long cours. Un suivi ophtalmologique régulier est recommandé afin de la dépister au stade infra-clinique. La dose d'HCQ administrée est également importante pour éviter les effets secondaires. Des études récentes ont suggéré qu'une dose supérieure à 5 mg/kg/j pourrait augmenter le risque de rétinopathie. Toutefois, à l'inverse une dose inférieure à 5 mg/kg/j pourrait exposer à une reprise d'activité de la maladie lupique. Le dosage sanguin peut permettre une optimisation du traitement, en dépistant les problèmes d'adhésion thérapeutique, mais aussi les problèmes de surdosage qui expose en effet à un risque de rétinopathie plus précoce. Les données cliniques sont globalement rassurantes quant à l'innocuité de l'HCQ pendant la grossesse des patientes lupiques. Les bénéfices cliniques pour le contrôle de la connectivite et le bon déroulement de la grossesse l'emportent sur les risques éventuels discutables. Hydroxychloroquine (HCQ) has recently been in the spotlight due to its use in the treatment of COVID-19, raising concerns about its cardiac tolerance. However, the effectiveness of HCQ in autoimmune diseases, particularly in systemic lupus, is well-established. It provides significant symptom improvement and prevents tissue damage. To prevent rare but potentially serious side effects, it is essential to monitor patients and consider the few contraindications. Retinopathy remains the most feared long-term complication. Regular ophthalmological follow-up is recommended to detect it at an early, subclinical stage. The administered dose of HCQ is also crucial to avoid side effects. Recent studies have suggested that a dose exceeding 5 mg/kg/day may increase the risk of retinopathy. On the other hand, a dose lower than 5 mg/kg/day may lead to a resurgence of lupus activity. Blood level monitoring can optimize treatment by detecting therapeutic adherence issues and potential overdose problems, which may lead to early-onset retinopathy. Clinical data are reassuring regarding the safety of HCQ during pregnancy in lupus patients. The clinical benefits for disease control and a successful pregnancy outweigh the disputed potential risks. [ABSTRACT FROM AUTHOR]

IntroductionT follicular (TFH) and peripheral helper (TPH) cells have been increasingly recognized as a pathogenic subset of CD4 T cells in systemic lupus erythematosus (SLE). The SLAM Associated Protein (SAP) regulates TFH and TPH function by binding to the co-stimulatory signaling lymphocyte activation molecule family (SLAMF) receptors that mediate T cell - B cell interactions. SAP and SLAMF are critical for TPH-dependent B cell maturation into autoantibody-producing plasma cells that characterize SLE pathogenesis. We hypothesized that SAP-expressing TPH cells are involved in the pathogenesis of lupus nephritis (LN).MethodsPeripheral blood mononuclear cells (PBMC) were isolated using density gradient separation from whole blood. Cells were stained for cell surface markers, followed by permeabilization and staining of intracellular SAP for spectral flow cytometry analysis. We also analyzed SAP expression from renal infiltrating LN T cells using the available single-cell RNA sequencing (scRNA seq) Accelerated Medicines Partnership (AMP) SLE dataset.ResultsPBMC from 30 patients with SLE (34 ± 10 years old, 83% female), including 10 patients with LN, were analyzed. We found an increase in total SAP-positive CD4 and CD8 T cells in SLE compared with controls (55.5 ± 2.6 vs. 41.3 ± 3.4, p=0.007, and 52.5 ± 3.0 vs. 39.2 ± 2.8, p=0.007 respectively). In CD4 T cells, the highest SAP expression was in the TPH subset. The frequency of SAP+TPH in circulation correlated with disease activity; SLE patients with renal disease had higher levels of circulating SAP+TPH that remained significant after adjusting for age, sex, race, low complements, and elevated anti-dsDNA (p=0.014). scRNA-seq data of renal infiltrating T cells in LN identified SAP expression to localize to the TFH-like CD4 cluster and GZMK+ CD8 cluster. Increased SAP expression in LN was associated with the differential expression of SLAMF3 and SLAMF7 and granzyme K and EOMES. The existence of two predominant SAP-expressing subsets, the TFH-like CD4 T cells, and GZMK+ effector CD8 T cells, was verified using scRNA-seq data from a human transcriptomic atlas of fifteen major organs.ConclusionThe expansion of SAP-expressing T helper cells was associated with LN in our cohort and verified using scRNA-seq data of renal infiltrating T cells. Improved SLAM and SAP signaling understanding can identify new therapeutic targets in LN.

Abstract Background Lupus nephritis and lupus erythematosus tumidus (LET) are uncommon manifestations of systemic lupus erythematosus (SLE), and their coexistence as the initial presentation of SLE is exceedingly rare. Here, we report such a case, emphasizing the diagnostic challenges and therapeutic implications of this unusual association. Case report A 38-year-old North African woman presented in Nephrology department with a history of lower extremity edema, fatigue, and weight loss of 3 kg in 4 weeks. Physical examination revealed LET lesions on the chest and the Neck. Laboratory investigations showed lymphopenia, low C3 and C4 complement levels, positive antinuclear antibodies, anti-dsDNA antibodies, and anti-SSA/Ro antibodies. Renal function tests showed normal serum creatinine and nephrotic proteinuria. Renal biopsy revealed Class V lupus nephritis. Skin biopsy confirmed the diagnosis of LET, with the presence of lymphohistiocytic infiltrates and dermal mucin. The patient was diagnosed with SLE based on the 2019 EULAR/ACR criteria and treated with prednisone (1 mg/kg/day) and hydroxychloroquine. She showed significant improvement in her cutaneous and renal symptoms at 6 and 12 months follow-up. Conclusion The rarity of the coexistence of LET and lupus nephritis as the initial manifestation of SLE, especially in the North African population, underscores the need for further research to elucidate the immunopathogenic mechanisms and prognostic factors associated with this association.

Abstract Background Systemic lupus erythematosus is a chronic multisystem disease that has a considerable morbidity and mortality. Rituximab is used in treating some severe manifestations of systemic lupus erythematosus; however, it may expose patients to serious infections. We report a case of post rituximab infective endocarditis as the second case in literature described in patients with SLE. Case presentation A 17-year-old male diagnosed as systemic lupus erythematosus with lupus nephritis and dilated cardiomyopathy received rituximab and underwent upper endoscopy and colonoscopy investigating iron deficiency anemia. Later on the patient developed septic shock secondary to infective endocarditis and passed away. Conclusions Infective endocarditis is a possible complication after rituximab therapy in lupus patients with lupus nephritis and dilated cardiomyopathy. Prophylactic antibiotics may be considered in those patients in the settings of gastrointestinal endoscopies.

Background: Lupus nephritis and lupus erythematosus tumidus (LET) are uncommon manifestations of systemic lupus erythematosus (SLE), and their coexistence as the initial presentation of SLE is exceedingly rare. Here, we report such a case, emphasizing the diagnostic challenges and therapeutic implications of this unusual association. Case report: A 38-year-old North African woman presented in Nephrology department with a history of lower extremity edema, fatigue, and weight loss of 3 kg in 4 weeks. Physical examination revealed LET lesions on the chest and the Neck. Laboratory investigations showed lymphopenia, low C3 and C4 complement levels, positive antinuclear antibodies, anti-dsDNA antibodies, and anti-SSA/Ro antibodies. Renal function tests showed normal serum creatinine and nephrotic proteinuria. Renal biopsy revealed Class V lupus nephritis. Skin biopsy confirmed the diagnosis of LET, with the presence of lymphohistiocytic infiltrates and dermal mucin. The patient was diagnosed with SLE based on the 2019 EULAR/ACR criteria and treated with prednisone (1 mg/kg/day) and hydroxychloroquine. She showed significant improvement in her cutaneous and renal symptoms at 6 and 12 months follow-up. Conclusion: The rarity of the coexistence of LET and lupus nephritis as the initial manifestation of SLE, especially in the North African population, underscores the need for further research to elucidate the immunopathogenic mechanisms and prognostic factors associated with this association. [ABSTRACT FROM AUTHOR]

Purpose: The association between COVID-19 and hypercoagulability is well established. This is a case of a patient with systemic lupus erythematosus (SLE) who developed unilateral renal vein thrombosis following COVID-19, the third case described in the international literature so far. Methods: Clinical, laboratory characteristics and outcomes of the patient were described in detail. Literature review was performed on MEDLINE database via Pubmed. Search items included COVID-19, renal infarction, and renal thrombosis. A total of fifty-three cases were located. Of these, only two patients had renal vein thrombosis but none of them carried a diagnosis of SLE. However, six cases have been published so far involving SLE patients in whom thromboembolic events developed following COVID-19, but none of them experienced renal vein thrombosis. Conclusion: The present case adds a new piece to the emerging puzzle of COVID-19 associated hypercoagulability, especially among patients with autoimmune diseases. [ABSTRACT FROM AUTHOR]

Sometimes, child’s rheumatic diseases are generating emergency type complications which, if not diagnosed in time, are life-threatening. Antiphospholipid syndrome in its severe form can induce coagulation disorders and acute organ failure, depending on location and extent. Systemic lupus erythematosus is frequently associated with this pathology and must be carefully investigated and monitored in the evolution of the patient, in order to benefit from early specific anticoagulant treatment, associated with chronic background immunosuppressive treatment. [ABSTRACT FROM AUTHOR]

Background: Systemic lupus erythematosus is a chronic multisystem disease that has a considerable morbidity and mortality. Rituximab is used in treating some severe manifestations of systemic lupus erythematosus; however, it may expose patients to serious infections. We report a case of post rituximab infective endocarditis as the second case in literature described in patients with SLE. Case presentation: A 17-year-old male diagnosed as systemic lupus erythematosus with lupus nephritis and dilated cardiomyopathy received rituximab and underwent upper endoscopy and colonoscopy investigating iron deficiency anemia. Later on the patient developed septic shock secondary to infective endocarditis and passed away. Conclusions: Infective endocarditis is a possible complication after rituximab therapy in lupus patients with lupus nephritis and dilated cardiomyopathy. Prophylactic antibiotics may be considered in those patients in the settings of gastrointestinal endoscopies. [ABSTRACT FROM AUTHOR]

La maladie de Castleman, lymphoprolifération rare, peut mimer un lupus systémique. Inversement, le lupus systémique peut se présenter telle une hémopathie. Dans ces cas, une histologie « Castleman-like » a été exceptionnellement décrite. Une patiente de 55 ans, traitée par méthotrexate pour un lupus arthrocutané, présentait des signes généraux, une polyadénopathie et des signes cliniques de poussée lupique. La biologie montrait une pancytopénie, un complément consommé et des anticorps anti-ADN positifs. Le PET-scanner objectivait une polyadénopathie hypermétabolique. La biopsie ganglionnaire décrivait des aspects « Castleman-like ». Un traitement par corticothérapie et azathioprine permettait une rémission complète. Le lupus systémique et la maladie de Castleman peuvent partager des éléments clinico-biologiques et histologiques communs. Dans ce cas, la présence d'éléments spécifiques de lupus systémique et la réponse à une corticothérapie à faible dose permettent de retenir le diagnostic de lupus systémique de forme Castleman-like et éviter une intensification thérapeutique. Castleman disease is a rare lymphoproliferation, which may mimic systemic lupus. Conversely, systemic lupus sometimes presents like an hematological malignancy. In these cases, a " Castleman-like " histology has been exceptionally described. A 55-year-old female treated by methotrexate for systemic lupus with skin and joint involvement presented weight loss, polyadenopathy and clinical signs of lupus flare. Biology showed pancytopenia, complement activation, and positive anti-DNA antibodies. PET/CT showed hypermetabolic polyadenopathy. The lymph node biopsy showed " Castleman-like " features. Treatment with corticosteroids and azathioprine resulted in complete remission. Systemic lupus and Castleman disease may share common clinical, biological, and histological features. The presence of specific elements of systemic lupus flare and the remission obtained by low-dose corticosteroids results in considering the diagnosis of Castleman-like systemic lupus and avoiding treatment intensification. [ABSTRACT FROM AUTHOR]

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune multi-system disorder frequently affecting black women of childbearing age. No published data exist on the obstetric outcomes in a Caribbean population. We analyzed pregnancy outcomes in an Afro-Caribbean cohort of women with SLE at a tertiary university hospital. A retrospective cohort study was performed of all pregnant women with SLE prior to pregnancy from January 1990 to December 2021 at the University Hospital of the West Indies (UHWI), Jamaica. Maternal rheumatologic, obstetric, fetal/neonatal data were analyzed. Descriptive statistical analyses were performed. To determine if outcomes were associated with various factors, Spearman's rho was followed by logistic regression analysis to estimate unadjusted odds ratios with statistical significance at p < 0.05. A total of 56 pregnancies in 47 women were identified with SLE. Live births were 87.5%, with 10.7% spontaneous miscarriages and no neonatal deaths. Prednisone was the most used drug in 67.9% of patients. 85% of women had an adverse outcome with an adverse fetal outcome occurring in 55% of cases. Prednisone was associated with an adverse fetal/neonatal outcome (Spearman's rho = 0.38; p =.004). In this first Caribbean series on SLE in pregnancy, reasonably successful pregnancy outcomes are achievable in Afro-Caribbean women managed in multidisciplinary centers. [ABSTRACT FROM AUTHOR]

Abstract Background Hearing loss can greatly affect the overall quality of life. Several studies have reported that patients with SLE may suffer from audio-vestibular manifestations. The aim of this study is to evaluate the influence of systemic lupus erythematosus (SLE) on hearing and association of hearing impairment with severity and duration of SLE. Results Pure-tone audiometry (PTA) (air conduction and bone conduction) thresholds showed significant elevation in SLE group than controls (P ≤ 0.05). It was observed also that there is a significant association between SLE severity and duration with sensorineural hearing loss (SNHL) and its degree. Conclusion SLE can lead to hearing loss, and there is a positive association of SLE severity and duration with degree of hearing loss.

The aims of the study were to (1) to characterize the breathing pattern and work of breathing during peak exercise in patients with SLE; (2) to examine the extent to which the breathing pattern and work of breathing impact the exercise capacity and fatigue. Forty-one women participated in the study (SLE: n = 23, median = 35, range = 21–57 years, control: n = 18, median = 38, range = 22–45 years). Each subject performed a treadmill cardiopulmonary exercise test (a modified Bruce treadmill protocol) ending with volitional exhaustion. Breathing mechanic was characterized by measures of expired minute volume (VE), tidal volume (Vt), respiratory rate (f), work of breathing, and cardiorespiratory fitness was quantified by measures of peak oxygen consumption (VO2) and time to exhaustion. Data presented as median and interquartile range (IQR). Women with SLE had lower Vt {1221 [488.8] mL/min vs. 1716 [453.1] mL; p =.006}, VE {58.9 [18.9] L/min vs 70 [28.1] L/min, p = 0.04} and increased breathing frequency {51.5 [10.8] vs 43.6 [37.8] bpm, p = 0.01} compared to the control group. The time to exhaustion and peak VO2 during the CPET were significantly reduced in those with SLE compared to controls {13.3 [10.2] vs 16.1 [2.2] min; p = 0.004}, {20 [6.1] mL/kg/min vs 26.6 [7] mL/kg/min p < 0.001}, respectively. Differences remained when the analyses were controlled for the observed differences in peak VO2. When the regression model adjusted for the peak VO2, it had been shown that Vt, WOB and f were explained variances in the fatigue severity by 64% [p < 0.001]. The decline in VE and Vt coupled with a decreased peak VO2, and work of breathing may have contributed to low cardiorespiratory fitness and fatigue in patients with systemic lupus erythematosus. [ABSTRACT FROM AUTHOR]

Treatment of systemic lupus erythematosus (SLE) currently employs agents with relatively unselective immunosuppressive properties. However, two target-specific biological drugs have been approved: belimumab (anti-B-cell-activating factor/BAFF) and anifrolumab (anti-interferon alpha receptor-1/IFNAR1). Here, we performed a comparative risk-benefit assessment for both drugs based on the role of BAFF and IFNAR1 in host defense and the pathogenesis of SLE and by considering the available data on safety and efficacy. Due to differences in target expression sites, anti-IFNAR1, but not anti-BAFF, might elicit organ-specific effects, consistent with clinical efficacy data. The IFNAR1 is specifically involved in innate and adaptive antiviral immunity in most cells of the body. Consistent with this observation, the available safety data obtained from patients negatively selected for LN and neuropsychiatric SLE, primary immunodeficiencies, splenectomy and chronic HIV, HBV, HCV infections suggest an increased risk for some viral infections such as varicella zoster and perhaps influenza. In contrast, BAFF is mainly involved in adaptive immune responses in lymphoid tissues, thus anti-BAFF therapy modulates SLE activity and prevents SLE flares without interfering with local innate host defense mechanisms and should only marginally affect immune memory to previous pathogen exposures consistent with the available safety data from SLE patients without chronic HIV, HBV or HCV infections. When using belimumab and anifrolumab, careful patient stratification and specific precautions may minimize risks and maximize beneficial treatment effects for patients with SLE. [ABSTRACT FROM AUTHOR]

Lupus nephritis (LN) has been described as having worse survival and renal outcomes in African-descent patients than Caucasians. We aimed to provide long-term population-based data in an Afro-descendant cohort of LN with high income and easy and free access to specialized healthcare. Study design: We performed a retrospective population-based analysis using data from 2002–2015 of 1140 renal biopsies at the University Hospital of Martinique (French West Indies). All systemic lupus erythematosus patients with a diagnosis of LN followed for at least 12 months in Martinique or who died during this period were included. Results: A total of 89 patients were included, of whom 68 (76.4%) had proliferative (class III or IV), 17 (19.1%) had membranous (class V), and 4 (4.5%) had class I or II lupus nephritis according to the ISN/RPS classification. At a mean follow-up of 118.3 months, 51.7% of patients were still in remission. The rates of end-stage renal disease were 13.5%, 19.1%, and 21.3% at 10, 15, and 20 years of follow-up, respectively, and mortality rates were 4.5%, 5.6%, and 7.9% at 10, 15, and 20 years of follow-up, respectively. Conclusions: The good survival of our Afro-descendant LN patients, similar to that observed in Caucasians, shades the burden of ethnicity but rather emphasizes and reinforces the importance of optimizing all modifiable factors associated with poor outcome, especially socioeconomics. [ABSTRACT FROM AUTHOR]

Le lupus érythémateux systémique (LES) est une maladie auto-immune multifactorielle complexe dépendant à la fois de facteurs intrinsèques et environnementaux. Parmi ces derniers, l'Epstein-Barr Virus (EBV) a depuis longtemps été évoqué comme potentiellement responsable dans l'installation puis dans l'activité de la maladie lupique. Il s'agit d'un herpès virus avec un tropisme très particulier pour les lymphocytes B et donc intimement lié au système immunitaire. L'infection à EBV précède de manière quasi-systématique l'installation de la maladie lupique et des données in vitro ou sur des modèles animaux suggèrent que la réponse anti-EBV pourrait être à l'origine de l'apparition d'auto-anticorps et de la maladie lupique chez certains sujets. Une fois le virus persistant dans l'organisme, il existe des anomalies des réponses anticorps et cellulaires contre l'EBV et les patients lupiques ont également un contrôle déficient de l'EBV, comme en témoignent les charges virales sanguines plus élevées observées chez ces malades. Or ce virus semble à même de favoriser l'activité de la maladie, notamment en favorisant la survie des lymphocytes B auto-réactifs et la production d'interféron-α qui sont deux phénomènes centraux dans la physiopathologie de la maladie lupique. Systemic lupus erythematosus (SLE) is a complex multifactorial autoimmune disease depending on both intrinsic and environmental factors. Among the latter, the Epstein-Barr Virus (EBV) has long been suggested as one of the responsible factors for the onset and activity of lupus disease. It is a herpes virus with a very specific tropism for B lymphocytes and therefore closely linked to the immune system. EBV infection almost always precedes the onset of lupus disease and in vitro data and animal models suggest that anti-EBV response may favor the development of autoantibodies and lupus disease in some subjects. Also, there are abnormalities in humoral and cellular responses to EBV and lupus patients have impaired control of EBV, with higher blood viral loads. Interstingly, this virus seems to be able to promote disease activity, by promoting the survival of autoreactive B lymphocytes and the production of interferon-α, which are two pivotal mechanisms in the pathophysiology of lupus disease. [ABSTRACT FROM AUTHOR]

Lung involvement in autoimmune diseases (AID) is uncommon, but may precede other organ manifestations. A diagnostic problem is chronicity presenting with lung fibrosis. A new category of interstitial pneumonia with autoimmune features for patients with clinical symptoms of AID and presenting with usual interstitial pneumonia (UIP) enables antifibrotic treatment for these patients. Hypersensitivity pneumonia (HP) and other forms of lung fibrosis were not included into this category. As these diseases based on adverse immune reactions often present with unspecific clinical symptoms, a specified pathological diagnosis will assist the clinical evaluation. We aimed to establish etiology-relevant differences of patterns associated with AID or HP combined with lung fibrosis. We retrospectively evaluated 51 cases of AID, and 29 cases of HP with lung fibrosis, and compared these to 24 cases of idiopathic pulmonary fibrosis (UIP/IPF). Subacute AID and HP most often presented with organizing pneumonia (OP), whereas chronicity was associated with UIP. Unspecified fibrosis was seen in a few cases, whereas NSIP pattern was rare. In 9 cases, the underlying etiology could not be defined. Statistically significant features differentiating chronic AID or HP from UIP/IPF are lymphocytic infiltrations into myofibroblastic/fibroblastic foci. Other features significantly associated with AID and HP were granulomas, isolated Langhans giant cells, and protein deposits, but seen in only a minority of cases. A combination of UIP with one of these features enabled a specific etiology-based diagnosis. Besides the antifibrotic drug regimen, additional therapies might be considered. [ABSTRACT FROM AUTHOR]

In recent years, we have seen an increase in thrombotic events in children, which creates difficulties in early diagnosis, especially in rare locations such as portal vein thrombosis. The most common cause is represented by antiphospholipid syndrome (APS), especially secondary to systemic lupus erythematosus (SLE). The investigation of the prothrombophilic pattern is mandatory in these patients, the association being possible. The therapeutic management is complex, in a multidisciplinary team, and will include, in addition to chronic anticoagulation, an effective immunosuppression to control the degree of activity of the lupus disease. [ABSTRACT FROM AUTHOR]

Linear discoid lupus erythematosus is a chronic disease of unknown etiology. It is characterized by erythematosus plaques that follow Blaschko's lines and is an unusual variant of discoid lupus erythematosus. The present review describes the case of a female patient who consulted for a lesion on the face and an alopecic area on the scalp associated with manifestations of systemic lupus erythematosus; an adequate response to pharmacological treatment was presented. The search for scientific articles for the development of this report was conducted in the following databases: ClinicalKey, Ovid, and PubMed. It is currently the first clinical case report described of linear discoid lupus erythematosus associated with systemic lupus erythematosus. A literature review will be conducted. [ABSTRACT FROM AUTHOR]

Though the exact causes of systemic lupus erythematosus (SLE) remain unknown, exposure to ultraviolet (UV) light is one of the few well-known triggers of cutaneous inflammation in SLE. However, the precise cell types which contribute to the early cutaneous inflammatory response in lupus, and the ways that UV dosing and interferons modulate these findings, have not been thoroughly dissected. Here, we explore these questions using the NZM2328 spontaneous murine model of lupus. In addition, we use iNZM mice, which share the NZM2328 background but harbor a whole-body knockout of the type I interferon (IFN) receptor, and wild-type BALB/c mice. 10-13-week-old female mice of each strain were treated with acute (300 mJ/cm 2 x1), chronic (100 mJ/cm 2 daily x5 days), or no UVB, and skin was harvested and processed for bulk RNA sequencing and flow cytometry. We identify that inflammatory pathways and gene signatures related to myeloid cells - namely neutrophils and monocyte-derived dendritic cells - are a shared feature of the acute and chronic UVB response in NZM skin greater than iNZM and wild-type skin. We also verify recruitment and activation of these cells by flow cytometry in both acutely and chronically irradiated NZM and WT mice and demonstrate that these processes are dependent on type I IFN signaling. Taken together, these data indicate a skewed IFN-driven inflammatory response to both acute and chronic UVB exposure in lupus-prone skin dominated by myeloid cells, suggesting both the importance of type I IFNs and myeloid cells as therapeutic targets for photosensitive patients and highlighting the risks of even moderate UV exposure in this patient population., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Seven of the 11 newer medications recently or soon to be approved to treat rheumatologic diseases discussed in this article are biologic agents and reflect the current ability of science to target specific components of the immune system. The other agents are molecules that are directed against specific immune pathway targets as well. All have shown superiority to placebo and in some cases have been compared to currently accepted therapies. Safety issues are generally centered around infections due to the immune-interrupting nature of these therapies., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background Rheumatic immune mediated inflammatory diseases (IMIDs) are associated with high risk of acute coronary syndrome. The long‐term prognosis of acute coronary syndrome in patients with rheumatic IMIDs is not well studied. Methods and Results We identified Medicare beneficiaries admitted with a primary diagnosis of myocardial infarction (MI) from 2014 to 2019. Outcomes of patients with MI and concomitant rheumatic IMIDs including systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, dermatomyositis, or psoriasis were compared with propensity matched control patients without rheumatic IMIDs. One‐to‐three propensity‐score matching was done for exact age, sex, race, ST‐segment–elevation MI, and non–ST‐segment–elevation MI variables and greedy approach on other comorbidities. The study primary outcome was all‐cause mortality. The study cohort included 1 654 862 patients with 3.6% prevalence of rheumatic IMIDs, the most common of which was rheumatoid arthritis, followed by systemic lupus erythematosus. Patients with rheumatic IMIDs were younger, more likely to be women, and more likely to present with non–ST‐segment–elevation MI. Patients with rheumatic IMIDs were less likely to undergo coronary angiography, percutaneous coronary intervention or coronary artery bypass grafting. After propensity‐score matching, at median follow up of 24 months (interquartile range 9–45), the risk of mortality (adjusted hazard ratio [HR], 1.15 [95% CI, 1.14–1.17]), heart failure (HR, 1.12 [95% CI 1.09–1.14]), recurrent MI (HR, 1.08 [95% CI 1.06–1.11]), and coronary reintervention (HR, 1.06 [95% CI, 1.01–1.13]) (P

Treatment of systemic lupus erythematosus (SLE) currently employs agents with relatively unselective immunosuppressive properties. However, two target-specific biological drugs have been approved: belimumab (anti-B-cell-activating factor/BAFF) and anifrolumab (anti-interferon alpha receptor-1/IFNAR1). Here, we performed a comparative risk-benefit assessment for both drugs based on the role of BAFF and IFNAR1 in host defense and the pathogenesis of SLE and by considering the available data on safety and efficacy. Due to differences in target expression sites, anti-IFNAR1, but not anti-BAFF, might elicit organ-specific effects, consistent with clinical efficacy data. The IFNAR1 is specifically involved in innate and adaptive antiviral immunity in most cells of the body. Consistent with this observation, the available safety data obtained from patients negatively selected for LN and neuropsychiatric SLE, primary immunodeficiencies, splenectomy and chronic HIV, HBV, HCV infections suggest an increased risk for some viral infections such as varicella zoster and perhaps influenza. In contrast, BAFF is mainly involved in adaptive immune responses in lymphoid tissues, thus anti-BAFF therapy modulates SLE activity and prevents SLE flares without interfering with local innate host defense mechanisms and should only marginally affect immune memory to previous pathogen exposures consistent with the available safety data from SLE patients without chronic HIV, HBV or HCV infections. When using belimumab and anifrolumab, careful patient stratification and specific precautions may minimize risks and maximize beneficial treatment effects for patients with SLE.

Systemic lupus erythematosus is a complex disease and can present with almost any organ involvement, including serosal inflammation. Our patient is not known to have any medical problems, presented for the first time with pseudo-pseudo Meigs' syndrome (PPMS), and after extensive workup to rule out other possibilities like infection and malignancy, she was found to have systemic lupus erythematosus. Several other cases have been reported in the literature; our patient had to have a pleural biopsy for completion of workup. She responded to prednisone and Immune suppression therapy (including mycophenolate mofetil (MMF) and Plaquenil).

Purpose: The association between COVID-19 and hypercoagulability is well established. This is a case of a patient with systemic lupus erythematosus (SLE) who developed unilateral renal vein thrombosis following COVID-19, the third case described in the international literature so far. Methods: Clinical, laboratory characteristics and outcomes of the patient were described in detail. Literature review was performed on MEDLINE database via Pubmed. Search items included COVID-19, renal infarction, and renal thrombosis. A total of fifty-three cases were located. Of these, only two patients had renal vein thrombosis but none of them carried a diagnosis of SLE. However, six cases have been published so far involving SLE patients in whom thromboembolic events developed following COVID-19, but none of them experienced renal vein thrombosis. Conclusion: The present case adds a new piece to the emerging puzzle of COVID-19 associated hypercoagulability, especially among patients with autoimmune diseases.

Computer-aided rational vaccine design (RVD) and synthetic pharmacology are rapidly developing fields that leverage existing datasets for developing compounds of interest. Computational proteomics utilizes algorithms and models to probe proteins for functional prediction. A potentially strong target for computational approach is autoimmune antibodies, which are the result of broken tolerance in the immune system where it cannot distinguish "self" from "non-self" resulting in attack of its own structures (proteins and DNA, mainly). The information on structure, function, and pathogenicity of autoantibodies may assist in engineering RVD against autoimmune diseases. Current computational approaches exploit large datasets curated with extensive domain knowledge, most of which include the need for many resources and have been applied indirectly to problems of interest for DNA, RNA, and monomer protein binding. We present a novel method for discovering potential binding sites. We employed long short-term memory (LSTM) models trained on FASTA primary sequences to predict protein binding in DNA-binding hydrolytic antibodies (abzymes). We also employed CNN models applied to the same dataset for comparison with LSTM. While the CNN model outperformed the LSTM on the primary task of binding prediction, analysis of internal model representations of both models showed that the LSTM models recovered sub-sequences that were strongly correlated with sites known to be involved in binding. These results demonstrate that analysis of internal processes of LSTM models may serve as a powerful tool for primary sequence analysis. [ABSTRACT FROM AUTHOR]

Background: Systemic Lupus Erythematosus (SLE) is an autoimmune disease with unknown aetiology. SLE attacks multiple organs with diverse clinical manifestations. Most patients get immunosuppressant therapy that suppresses immune system, causing the body to be susceptible to infection. Objective: to describe clinical manifestations, laboratory abnormalities, and incidence of infections in SLE patients hospitalized at Dr. Soetomo General Academic Hospital, Surabaya, Indonesia in 2016. Materials and Methods: Cross-sectional descriptive observational study used medical records of 273 SLE patients hospitalized at Dr. Soetomo General Academic Hospital, Surabaya, Indonesia in 2016. Results: Clinical manifestations found in this study were malar rash 7.33%, discoid rash 2.93%, oral ulcer 8.42%, allopecia 16.48%, arthritis 26.74%, serositis 13.19%, kidney 35.9%, neurology 24.91%, anemia 73.71%, leucopenia 32.67%, lymphopenia 76.89%, and thrombocytopenia 33.86%. Laboratory abnormalities found in this study were hematology (anemia 73.71%, leucopenia 32.67%, lymphopenia 76.89%, thrombocytopenia 33.86%), kidney function (high serum creatinine levels 39.66%, high BUN levels 41.2%, hypoalbuminemia 62.6%), urine (proteinuria 68.21%, hematuria 51.79%) and liver function (high ALT levels 36.65%, high AST levels 29.86%). Infection occurred in 33.7% patients. The most common infections were pneumonia (70.65%), urinary tract infections (51.09%), and sepsis (35.87%). Conclusion: The most common clinical manifestations experienced by SLE patients are hematological disorder, kidney disorder, and arthritis. Prominent laboratory abnormalities are anemia, lymphopenia, and proteinuria. Infection is a common complication, with the most common types pneumonia, urinary tract infection, and sepsis.