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Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease characterised by the presence of autoantibodies towards nuclear antigens, immune complex deposition, and chronic inflammation at classic target organs such as skin, joints, and kidneys. Despite substantial advances in the diagnosis and management of SLE, the burden of disease remains high. It is important to appreciate the typical presentations and the diagnostic process to facilitate early referral and diagnosis for patients. In most patients, constitutional, mucocutaneous, and musculoskeletal symptoms represent the earliest complaints; these symptoms can include fatigue, lupus-specific rash, mouth ulcers, alopecia, joint pain, and myalgia. In this Seminar we will discuss a diagnostic approach to symptoms in light of the latest classification criteria, which include a systematic evaluation of clinical manifestations (weighted within each domain) and autoantibody profiles (such as anti-double-stranded DNA, anti-Sm, hypocomplementaemia, or antiphospholipid antibodies). Non-pharmacotherapy management is tailored to the individual, with specific lifestyle interventions and patient education to improve quality of life and medication (such as hydroxychloroquine or immunosuppressant) adherence. In the last decade, there have been a few major breakthroughs in approved treatments for SLE and lupus nephritis, such as belimumab, anifrolumab, and voclosporin. However the disease course remains variable and mortality unacceptably high. Access to these expensive medications has also been restricted across different regions of the world. Nonetheless, understanding of treatment goals and strategies has improved. We recognise that the main goal of treatment is the achievement of remission or low disease activity. Comorbidities due to both disease activity and treatment adverse effects, especially infections, osteoporosis, and cardiovascular disease, necessitate vigilant prevention and management strategies. Tailoring treatment options to achieve remission, while balancing treatment-related comorbidities, are priority areas of SLE management.

Systemic lupus erythematosus (SLE) is an immune-mediated multi-systemic disease characterized by a wide variability of clinical manifestations and a course frequently subject to unpredictable flares. Despite significant advances in the understanding of the pathophysiology and optimization of medical care, patients with SLE still have significant mortality and carry a risk of progressive organ damage accrual and reduced health-related quality of life. New tools allow earlier classification of SLE, whereas tailored early intervention and treatment strategies targeted to clinical remission or low disease activity could offer the opportunity to reduce damage, thus improving long-term outcomes. Nevertheless, the early diagnosis of SLE is still an unmet need for many patients. Further disentangling the SLE susceptibility and complex pathogenesis will allow to identify more accurate biomarkers and implement new ways to measure disease activity. This could represent a major step forward to find new trials modalities for developing new drugs, optimizing the use of currently available therapeutics and minimizing glucocorticoids. Preventing and treating comorbidities in SLE, improving the management of hard-to-treat manifestations including management of SLE during pregnancy are among the remaining major unmet needs. This review provides insights and a research agenda for the main challenges in SLE.

ObjectivesTo update the EULAR recommendations for the management of systemic lupus erythematosus (SLE) based on emerging new evidence.MethodsAn international Task Force formed the questions for the systematic literature reviews (January 2018–December 2022), followed by formulation and finalisation of the statements after a series of meetings. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned, and participants finally provided their level of agreement with each item.ResultsThe Task Force agreed on 5 overarching principles and 13 recommendations, concerning the use of hydroxychloroquine (HCQ), glucocorticoids (GC), immunosuppressive drugs (ISDs) (including methotrexate, mycophenolate, azathioprine, cyclophosphamide (CYC)), calcineurin inhibitors (CNIs, cyclosporine, tacrolimus, voclosporin) and biologics (belimumab, anifrolumab, rituximab). Advice is also provided on treatment strategies and targets of therapy, assessment of response, combination and sequential therapies, and tapering of therapy. HCQ is recommended for all patients with lupus at a target dose 5 mg/kg real body weight/day, considering the individual’s risk for flares and retinal toxicity. GC are used as ‘bridging therapy’ during periods of disease activity; for maintenance treatment, they should be minimised to equal or less than 5 mg/day (prednisone equivalent) and, when possible, withdrawn. Prompt initiation of ISDs (methotrexate, azathioprine, mycophenolate) and/or biological agents (anifrolumab, belimumab) should be considered to control the disease and facilitate GC tapering/discontinuation. CYC and rituximab should be considered in organ-threatening and refractory disease, respectively. For active lupus nephritis, GC, mycophenolate or low-dose intravenous CYC are recommended as anchor drugs, and add-on therapy with belimumab or CNIs (voclosporin or tacrolimus) should be considered. Updated specific recommendations are also provided for cutaneous, neuropsychiatric and haematological disease, SLE-associated antiphospholipid syndrome, kidney protection, as well as preventative measures for infections, osteoporosis, cardiovascular disease.ConclusionThe updated recommendations provide consensus guidance on the management of SLE, combining evidence and expert opinion.

BackgroundMusculoskeletal (MSK) diseases are expected to have a growing impact worldwide.ObjectiveTo analyse the worldwide burden of MSK diseases from 2000 to 2015.MethodsDisability-adjusted life years (DALYs), which combines the years of life lost (YLLs) and the years lived with disability (YLDs), were extracted for 183 countries from the WHO Global Health Estimates Database. We analysed the median proportion of DALYS, YLLs and YLDs for MSK diseases (ICD-10: M00–M99) among the 23 WHO categories of diseases. Mixed models were built to assess temporal changes.ResultsWorldwide, the total number of MSK DALYs increased significantly from 80,225,634.6 in 2000 to 107,885,832.6 in 2015 (p < 0.001), with the total number of MSK YLDs increasing from 77,377,709.4 to 103,817,908.4 (p = 0.0008) and MSK diseases being the second cause of YLDs worldwide. YLLs due to MSK diseases increased from 2,847,925.2 to 4,067,924.2 (p = 0.03). In 2015, the median proportion of DALYs attributed to MSK diseases was 6.66% (IQR: 5.30 – 7.88) in Europe versus 4.66% (3.98 – 5.59) in the Americas (p < 0.0001 vs Europe), 4.17% (3.14 – 6.25) in Asia (p < 0.0001), 4.14% (2.65 – 5.57) in Oceania (p = 0.0008) and 1.33% (1.03 – 1.92) in Africa (p < 0.0001). We observed a significant correlation (r = 0.85, p < 0.0001) between the proportion of MSK DALYs and the gross domestic product per capita for the year 2015.ConclusionsThe burden of MSK diseases increased significantly between 2000 and 2015 and is high in Europe. These results are crucial to health professionals and policy makers to implement future health plan adjustments for MSK diseases.

The antimalarial hydroxychloroquine (HCQ) has demonstrated several crucial properties for the treatment of systemic lupus erythematosus (SLE). Herein, we reviewed the main HCQ pharmacologic features, detailed its mechanism of action, and summarized the existing guidelines and recommendations for HCQ use in rheumatology with a systematic literature search for the randomized controlled trials focused on lupus. HCQ has been shown to decrease SLE activity, especially in mild and moderate disease, to prevent disease flare and to lower the long-term glucocorticoid need. The numerous benefits of HCQ are extended to pregnancy and breastfeeding period. Based on cohort studies, antithrombotic and metabolic HCQ’s effects were shown, including lipid-lowering properties, which might contribute to an improved cardiovascular risk. Moreover, early HCQ use in antinuclear antibodies positive individuals might delay the progression to SLE. Finally, HCQ has a significant favorable impact on long-term outcomes such as damage accrual and mortality in SLE. Based on these multiple benefits, HCQ is now the mainstay long-term treatment in SLE, recommended by current guidelines in all patients unless contraindications or side effects. The daily dose associated with the best compromise between efficacy and safety is matter of debate. The concern regarding retinal toxicity rather than proper efficacy data is the one that dictated the daily dosage of ⩽5 mg/kg/day actual body weight currently agreed upon.

A patient pathway is the patient experience from the first symptom through the initial referral for diagnosis, treatment and follow-up, and includes diverse aspects of disease management, such as holistic support and prevention of complications. Among the most significant challenges in systemic lupus erythematosus (SLE)1 are the excessive diagnosis delay and the lack of coordinated care. At our national reference center in Strasbourg (France), we have conducted a series of focus groups with healthcare professionals and SLE patients. Based on the collected data, the most impactful disruption points in SLE patient pathways were identified.2 A novel framework to improve individual patient pathways in SLE was developed, discussed and validated during a consensus meeting with representative stakeholders. Six main disruptions in optimal SLE patient pathways were identified: (1) appropriate and timely referral strategy for SLE diagnosis; (2) the need for a dedicated consultation during which the diagnosis of SLE would be communicated, and following which clarifications and psychological support offered; (3) individualized patient pathways with coordinated care based on organ involvement, disease severity and patient preference; (4) improved therapeutic patient education; (5) prevention of complications such as infections, osteoporosis and cancer; (6) and additional patient support. These disruption points are valuable knowledge, which may be used to improve individual patient pathways in SLE. These data may be of valuable interest to patients with SLE, their physicians, health organizations and policy makers.Felten R, et al. 10 most important contemporary challenges in the management of SLE. Lupus Sci Med. 2019 Jan 10;6(1):e000303. doi: 10.1136/lupus-2018-000303. Schlencker A, et al. Improving patient pathways for systemic lupus erythematosus: a multistakeholder pathway optimisation study. Lupus Sci Med. 2022 May;9(1):e000700. doi: 10.1136/lupus-2022-000700.Learning ObjectivesExplain the key concept of patient pathwaysDescribe how patient pathways can be mapped in systemic lupusIdentify the main disruption points in lupus patient pathwaysDescribe how to improve lupus patient pathways

Ice is a highly transparent material in the visible. According to the most widely used database (IA2008; Warren and Brandt, 2008), the ice absorption coefficient reaches values lower than 10−3 m−1 around 400 nm. These values were obtained from a vertical profile of spectral radiance measured in a single snow layer at Dome C in Antarctica. We reproduced this experiment using an optical fiber inserted in the snow to record 56 profiles from which 70 homogeneous layers were identified. Applying the same estimation method on every layer yields 70 ice absorption spectra. They present a significant variability but absorption coefficients are overall larger than IA2008 by 1 order of magnitude at 400–450 nm. We devised another estimation method based on Bayesian inference that treats all the profiles simultaneously. It reduces the statistical variability and confirms the higher absorption, around 2  ×  10−2 m−1 near the minimum at 440 nm. We explore potential instrumental artifacts by developing a 3-D radiative transfer model able to explicitly account for the presence of the fiber in the snow. The simulation shows that the radiance profile is indeed perturbed by the fiber intrusion, but the error on the ice absorption estimate is not larger than a factor of 2. This is insufficient to explain the difference between our new estimate and IA2008. The same conclusion applies regarding the plausible contamination by black carbon or dust, concentrations reported in the literature are insufficient. Considering the large number of profiles acquired for this study and other estimates from the Antarctic Muon and Neutrino Detector Array (AMANDA), we nevertheless estimate that ice absorption values around 10−2 m−1 at the minimum are more likely than under 10−3 m−1. A new estimate in the range 400–600 nm is provided for future modeling of snow, cloud, and sea-ice optical properties. Most importantly, we recommend that modeling studies take into account the large uncertainty of the ice absorption coefficient in the visible and that future estimations of the ice absorption coefficient should also thoroughly account for the impact of the measurement method.