Lupus Science & Medicine最新文献

Objectives: Some patients with SLE or Gougerot-Sjögren's disease (GSD) receive long-term treatment with hydroxychloroquine (HCQ), sometimes combined with immunosuppressive therapy (IS). This study sought to assess whether long-term HCQ therapy that had been initiated long before the COVID-19 pandemic had a protective or adverse effect on COVID-19 risk, severity of infection or immunity protection.

Methods: This prospective multicentre study included 547 patients with SLE, GSD, autoimmune hepatitis, primary biliary cholangitis or cured viral hepatitis C divided into four groups according to HCQ (+/-) and IS (+/-) intake prior to the pandemic: HCQ+IS+ (n=112), HCQ+IS- (n=121), HCQ-IS+ (n=115) and HCQ-IS- (n=199). When COVID-19 vaccination was possible, patients were vaccinated as recommended. Vaccination efficacy was prospectively assessed on the basis of the postvaccination antibody titre.

Results: Compared with HCQ+IS+ patients, HCQ-IS+ patients had a decreased risk of COVID-19 infection (p<0.001). Compared with HCQ+IS+ patients, HCQ-IS- patients had a decreased risk of contracting COVID-19 (p<0.001). Patients in the HCQ-IS+ or HCQ-IS- group had a lower risk of symptomatic or severe infection than HCQ+IS+ patients did (p=0.001 and p<0.001, respectively). Only patients who had two or more exposures (to vaccine and/or infection) had an increased likelihood of COVID-19 immunity after the last dose (p<0.001).

Conclusions: HCQ treatment that was initiated before the pandemic did not protect against COVID-19 infection. Moreover, non-exposure to HCQ treatment (combined or not with IS) was associated with decreased risk of COVID-19 infection and of developing a symptomatic or severe infection. HCQ and IS do not influence the vaccine response. Only two or more doses of vaccine result in a good vaccine response.

Trial registration number: NCT04481633.

Background: SLE is prevalent in Saudi Arabia, with numerous studies focusing on SLE in adult patients. However, there is a lack of comprehensive studies summarising the extrarenal manifestations of SLE in this population. This study aims to assess the variability in the prevalence rates of extrarenal manifestations of SLE across different cities in Saudi Arabia and to emphasise the need for a national registry to better understand the overall disease burden in the region.

Methods: We conducted a systematic review of articles with no time restrictions, including studies from databases such as Medline, ScienceDirect, EBSCO and PubMed up to July 2024. The review process involved screening, data extraction and quality assessment in duplicate. Only observational or experimental studies focusing on extrarenal manifestations in adult patients with SLE in Saudi Arabia were included. The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist for systematic reviews to ensure a rigorous and comprehensive evaluation.

Results: A total of 35 studies were included, primarily retrospective cohort studies. Riyadh showed the highest number of publications over time. Musculoskeletal involvement in SLE ranged from 2% to 100%, with most studies reporting 46%-85%. Mucocutaneous manifestations, including discoid rash (5%-100%), malar rash (up to 79%) and photosensitivity (6.12%-29.3%), varied widely. Raynaud's phenomenon was noted at 4.5%-15.2%. Constitutional symptoms were more common in early-onset SLE, while serositis and cardiopulmonary issues showed variability. Neuropsychiatric symptoms, especially depression, reached up to 67.6%.

Conclusion: This study explores the prevalence of extrarenal manifestations of SLE among adult Saudi patients, highlighting significant regional variability in musculoskeletal, dermatological, cardiovascular and neurological symptoms. It addresses a gap in the literature for a region where autoimmune diseases are a growing public health concern. The findings emphasise the need for population-based studies to investigate environmental, genetic and lifestyle factors influencing SLE progression.

The Systemic Lupus International Collaborating Clinics (SLICC) is an international research group dedicated to promoting collaboration among scientific investigators in the study of systemic lupus erythematosus (SLE). Currently, most SLICC members are based in North America and Europe, with limited representation from other regions. SLICC recognises the importance of expanding its global collaborations and representation to ensure that its research accurately reflects the global burden of SLE and provides equal benefit to all patients with SLE worldwide. Given that SLICC currently lacks representation from the African continent, an opportunity was identified to convene a meeting bringing together lupus physicians with experience providing clinical care and conducting lupus research in Africa, along with members of the SLICC group. The purpose of the meeting was to share information regarding SLE in Africa, to discuss recent innovations and current challenges in the region and to explore future collaborations between SLICC members and colleagues in Africa in the areas of SLE clinical care, research and education. This meeting report highlights information presented during the seminar as well as a discussion of next steps moving forward.

Background: To evaluate the mortality patterns of SLE and the associated risk factors in Koreans.

Methods: Using the National Health Insurance database spanning 2008 to 2018, incident cases of SLE in patients aged 10-79 years were included. We analysed the all-cause mortality and cause-specific mortality, stratifying by sex and age. The mortality rate (MR) was calculated as the number of deaths per 100 000 person-years (PYs). The causes of death were identified by the International Classification of Diseases, 10th Revision codes during hospitalisation or emergency visit prior to death. A generalised estimating equation model was employed for risk factor analysis.

Results: In total, 11 375 incident SLE cases among patients with an average age of 42.3±16.7 years were recruited (86.1% female). During 57 658 PYs, 728 deaths occurred (MR 1262.62/100 000 PYs). The MR among men (2718.86/100 000 PYs) exceeded that among women (1060.57/100 000 PYs). The leading causes of death were SLE-related conditions (381.56/100 000 PYs), cardiovascular disease (CVD) (202.92/100 000 PYs), cancer (175.17/100 000 PYs) and infection (143.95/100 000 PYs). Of the SLE-related mortality, the key risk factors were pulmonary complications, such as pulmonary alveolar haemorrhage (OR 9.93), pulmonary arterial hypertension (OR 3.77) and interstitial lung disease (OR 3.27).

Conclusions: Among Korean patients with SLE, SLE-related conditions were the leading causes of mortality. However, CVD and cancer were also identified as the main causes of mortality. Furthermore, pulmonary manifestations were significantly associated with SLE-related mortality.

Objective: To assess the daily and weight-adjusted dosages of hydroxychloroquine (HCQ) and the effects on long-term remission in the Lupus-Cruces cohort.

Methods: Observational study of routine clinical care data. We selected inception patients treated with HCQ with at least 5 years of follow-up. Prolonged remission was achieved when patients fulfilled definitions of remission in systemic lupus erythematosus remission criteria in five consecutive yearly visits. The associations between the weight-adjusted dose of HCQ during 5 years and prolonged remission were analysed. We also investigated the associations between prednisone doses, immunosuppressives (IS) and other antimalarial use with HCQ doses.

Results: 150 inception patients fulfilled the inclusion criteria. The mean starting dose of HCQ was 206 mg/day. The mean weight-adjusted starting dose of HCQ was 3.1 mg/kg/day with no patients treated with doses ≥5 mg/kg/day. Treatment with HCQ was maintained during the whole 5-year follow-up time in 147 patients (98%). The mean dose of HCQ during the 5-year follow-up was 194.6 mg/day (2.9 mg/kg/day). 108 patients (72%) were in prolonged remission. The mean weight-adjusted dose of HCQ per patient did not differ between those who did and did not achieve prolonged remission (2.9 vs 3 mg/kg/day, p=0.5). The dose of prednisone per patient (mean 2.3 mg/day during the 5-year follow-up) did not differ according to the weight-adjusted dose of HCQ. The mean weight-adjusted HCQ dose during the whole follow-up was the same in patients treated or not with IS or with mepacrine.

Conclusions: With the use of HCQ at stable doses of 200 mg/day (or 3.0-3.5 mg/kg/day) as the background therapy in patients with systemic lupus erythematosus, the majority of patients achieved prolonged remission.

Objective: To develop a Register-Based Organ Damage Index (RBODI) in SLE, and evaluate its accuracy in estimating Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI) scores. Additionally, to describe organ damage accrual and associations with mortality in a Swedish population-based nationwide cohort.

Methods: SDI items were translated into diagnosis, treatment and procedural codes retrieved from Swedish health registers. RBODI was calculated using the same rules as the SDI and its accuracy was evaluated using SDI data from the Clinical Lupus Register in North-Eastern Gothia cohort as the gold standard. Among newly diagnosed patients with SLE from Sweden (2005-2021), we estimated 5-year risks of organ damage, and adjusted HRs of first RBODI-based organ damage accrual associated with patient characteristics. Lastly, we estimated the association between RBODI-based organ damage within 5 years of diagnosis and mortality.

Results: The evaluation cohort included 271 prevalent cases (65.3% developed organ damage). RBODI had a positive predictive value of 90%, sensitivity 80% and specificity 83%. Among 4441 newly diagnosed patients with SLE, 40% developed organ damage within 5 years. Males had a 30% higher risk of developing damage compared with females (HR 1.3) and older individuals (>45 years old compared with younger) had more than threefold higher risk (HR 3.3). Early development of organ damage was associated with a 2.1-fold higher risk of mortality.

Conclusion: Our novel RBODI accurately estimates SDI scores and describes long-term trends in damage accrual in the largest cohort of incident SLE to date. The strong association between early damage accrual and mortality highlights the need for efficient prevention strategies.

Background: Oral glucocorticoids (OCS) remain one of the most important treatments for SLE but are associated with damage. Evidence regarding the real-world use of OCS in nationwide SLE populations is currently lacking. The aim of this study was to analyse OCS use and SLE treatments in French patients with SLE at the national level.

Methods: The nationwide French health insurance claims database, which contains pseudonymised data for ≈66 million people, was used. Prevalent patients with SLE (International Classification of Diseases, 10th Revision code M32, recorded as a chronic condition or associated with hospital stay) were identified over the year 2019. SLE treatments were captured through actual drug deliveries by pharmacies and mean daily OCS doses (prednisone equivalent) were calculated for the year 2019.

Results: The 2019 French prevalent SLE population comprised 31 852 patients (86.3% of women, with a mean age of 49.7 (±15.9) years) with a mean disease duration of 7.1 (±6.2) years. Among these, 48.3% were treated with OCS. The mean daily OCS dose was ≤5 mg/day in 35.9%, more than 5 mg but <7.5 mg/day in 6.4% and ≥7.5 mg/day in 6.0%. The use of other SLE treatments was significantly increased in patients with higher doses of OCS (p<0.0001). Potential complications of OCS, including cardiovascular diseases, infections and osteoporosis, were significantly increased in patients with SLE receiving more than 5 mg of OCS per day (p<0.0001, for all). Strikingly, 13.6% of patients receiving mean daily OCS doses >5 mg/day were not treated with antimalarial, immunosuppressant or biologic drugs for SLE.

Conclusions: In total, 48.2% of French patients with SLE were treated with OCS in 2019, including 12.4% at a mean dose >5 mg/day, with an increased risk of OCS complications and a limited use of antimalarials, immunosuppressants or biologics. These results highlight the urgent need for the implementation of more robust OCS-sparing strategies in SLE.

Objective: To investigate the clinical features and treatment outcomes of anti-leucine-rich glioma-inactivated 1 (anti-LGI1) encephalitis in patients with SLE.

Methods: Between October 2014 and April 2024, serum or cerebrospinal fluid samples were collected from 332 patients with SLE suspected of autoimmune encephalitis. Cell-based assays were used to detect autoimmune antibodies, including anti-LGI1 antibodies. Four patients tested positive for anti-LGI1 antibodies, and their clinical, radiological and treatment data were analysed.

Results: All four patients exhibited signs of limbic encephalitis, including short-term memory deficits, seizures and psychiatric disturbances. Two cases also presented with faciobrachial dystonic seizures. MRI findings revealed hyperintense basal ganglia lesions in two patients. Treatment with corticosteroids, intravenous immunoglobulin and mycophenolate mofetil led to significant improvement in three patients, with no relapses during a follow-up period ranging from 33 to 60 months. One patient succumbed to pneumonia despite initial improvement of neurological function.

Conclusion: Screening for anti-LGI1 antibodies in patients with neuropsychiatric systemic lupus erythematosus (NPSLE) is crucial when limbic encephalitis presents, as it enables timely and effective treatment, potentially improving patients' outcomes. Additional basic and clinical research is required to clarify the pathogenic role of these antibodies in NPSLE.

Objectives: To evaluate the functional impact of a novel DNASE1L3 variant (c.572A>G, p.Asn191Ser) in three families with SLE and hypocomplementaemic urticarial vasculitis (HUV) from the United Arab Emirates.

Methods: Whole-exome sequencing was performed on affected patients and findings were confirmed using Sanger sequencing in family members. DNASE1L3 protein expression, secretion and enzymatic activity were assessed in HEK293 cell lines. Plasma smear assay for neutrophil extracellular traps (NETs) was evaluated in patients, family members and healthy control.

Results: A total of seven patients diagnosed with both SLE and HUV were identified from three unrelated families. All affected individuals were found to carry a homozygous c.572A>G, p.Asn191Ser (191S) variant in DNASE1L3. The variant 191S was shown to impact the secretion and activity of DNASE1L3. Patients homozygous for 191S variant had significantly higher burden (p=0.0409) of NET structure in comparison to heterozygous and healthy control.

Conclusions: We functionally evaluated the effect of a novel DNASE1L3 (c.572A>G, p.Asn191Ser) in familial SLE with a consistent pattern of HUV across seven patients. This variant resulted in impaired secretion and enzymatic activity of DNASE1L3 along with increased NETosis in patients with homozygous genotype.