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Ethnicity-specific patterns of epigenetic age acceleration in rheumatoid arthritisRheumatoid arthritis (RA) is an age-related chronic inflammatory disease which may include accelerated biological ageing processes in its pathogenesis. To determine if increased biological age is associated with risk of RA and/or is present once disease is established. We used DNA methylation to compare biological age (epigenetic age) of immune cells in adults at risk of RA and those with confirmed RA, including twins discordant for RA. The established RA studies were secondary analyses of existing DNA methylation data. Sub-group analysis considered the influence of ethnicity. Four epigenetic clocks were used to determine DNA methylation age. DNA methylation age was no different in adults at risk of RA in the Leiden Clinically Suspect Arthralgia (CSA) cohort (n = 38 developed RA, n = 24 did not), and there was also no difference in DNA methylation age between 77 UK twins discordant for RA, or adults with established RA from the Swedish EIRA cohort (n = 342) compared to healthy controls (n = 328). A sub-group analysis of RA patients of South Asian ethnicity (10 RA patients, 14 healthy controls) showed DNA methylation age acceleration of 3.3 years (p = 0.00014) using the mean DNA methylation age of four epigenetic clocks. Our study suggests that epigenetic age acceleration may be differentially influenced by South Asian ethnicity, but that RA was not generally associated with accelerated epigenetic age. The higher epigenetic age in the South Asian patients may explain the earlier age of onset in this minority ethnic population.
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Patient-reported outcomes as early warning signs of flare following drug cessation in rheumatoid arthritisObjectives: Drug withdrawal in rheumatoid arthritis (RA) in remission can reduce toxicity, but with the risk of flare which requires close monitoring. We explored the potential of patient-reported outcomes (PROs) for flare detection among RA patients in sustained remission after conventional synthetic disease-modifying antirheumatic drug (csDMARD) cessation. Methods: Four PROs (Factors that Limit sustAined Remission in rhEumatoid arthritis (FLARE-RA), EuroQol-5 Dimensions (EQ5D), Routine Assessment of Patient Index Data-3 (RAPID-3) and RA Flare Questionnaire (RA-FQ)) were captured at baseline and at sequential visits until time-of-flare or end of 6-month follow-up as part of the BIO-FLARE prospective cohort study. Flare was defined as any of (i) Disease Activity Score 28 (DAS28)-C reactive protein (CRP) ≥3.2 at any visit, (ii) DAS28-CRP≥2.4 on two visits within 2 weeks or (iii) resuming DMARD and/or steroid therapy despite DAS28-CRP<2.4. Cox regression models with time-varying covariates were fitted to evaluate associations between PRO changes and likelihood of flare. Receiver-operating characteristic (ROC) curves enabled discriminatory changes in each PRO to be compared as a means of identifying flare. Results: 58/121 (47.9%) participants (70.1% females, mean age 64.8 years) experienced a flare. A 1-point change in each PRO score was strongly associated with flare development in the multivariate Cox regression model (p<0.001 in each case). ROC curve analysis confirmed that monitoring adverse changes in PROs from baseline offered robust discriminatory utility for identifying flare occurrence. This was most evident for RA-FQ and FLARE-RA (both areas under the curves 0.90, 95% CI 0.84 to 0.96; p=0.001); for example, an RA-FQ increment of ≥5.5 from baseline identified objective flare with positive and negative predictive values of 80% and 91%, respectively. Conclusions: Our data support the potential value of remote PRO monitoring of RA patients in drug-free remission to identify flare occurrence.
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Vamorolone : a novel metabolism resistant steroid that suppresses joint destruction in chronic polyarthritis with reduced systemic side effectsObjectives: Vamorolone, a dissociated steroidal compound with reduced side effects, offers a promising alternative to traditional glucocorticoids for inflammatory diseases. Unlike conventional glucocorticoids, vamorolone lacks the hydroxyl or ketone groups required for metabolism by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), a key enzyme that modulates glucocorticoid activity. This study investigates vamorolone's resistance to 11β-HSD1 metabolism and assesses its therapeutic efficacy in the murine tumour necros factor-alpha-overexpressing (TNFtg) model of polyarthritis. Methods: 11β-HSD1 metabolism and action were examined in Hs68 and primary leucocyte culture. Vamorolone 20 mg/kg/day, prednisolone (standard of care) or vehicle were administered by gavage to TNFtg or TNFtg 11β-HSD1 knock-out (TNFtg11BKOKO) animals. Body weight and disease severity were scored daily, and markers of inflammation, joint destruction and side effects assessed at day 56 of age. Results: Vamorolone was entirely resistant to 11β-HSD1 metabolism in vitro. Vamorolone demonstrated comparable anti-inflammatory actions in TNFtg mice, with a comparable reduction in joint inflammation, serum interleukin-6 (IL-6) and synovitis relative to prednisolone. However, vamorolone-treated mice did not experience typical glucocorticoid side effects, including adrenal atrophy, body weight reduction, muscle wasting or inhibition of anabolic bone metabolism. These benefits persisted in 11β-HSD1 knockout mice, indicating that the efficacy of vamorolone is largely independent of 11β-HSD1 metabolism. Conclusion: The findings suggest that at the effective anti-inflammatory dose examined in this study, vamorolone possesses a reduced profile of deleterious systemic effects relative to prednisolone. Whilst highlighting its potential for broader clinical application in inflammatory conditions, it remains unclear whether these side effects would remain mild at markedly higher doses.
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Clinical predictors of flare and drug-free remission in rheumatoid arthritis : preliminary results from the prospective BIO-FLARE experimental medicine studyObjectives: Huge advances in rheumatoid arthritis (RA) treatment mean an increasing number of patients now achieve disease remission. However, long-term treatments can carry side effects and associated financial costs. In addition, some patients still experience painful and debilitating disease flares, the mechanisms of which are poorly understood. High rates of flare and a lack of effective prediction tools can limit attempts at treatment withdrawal. The BIOlogical Factors that Limit sustAined Remission in rhEumatoid arthritis (BIO-FLARE) experimental medicine study was designed to study flare and remission immunobiology. Here, we present the clinical outcomes and predictors of drug-free remission and flare, and develop a prediction model to estimate flare risk. Design, setting and participants: BIO-FLARE was a multicentre, prospective, single-arm, open-label experimental medicine study conducted across seven National Health Service Trusts in the UK. Participants had established RA in clinical remission (disease activity score in 28 joints with C reactive protein (DAS28-CRP)<2.4) and were receiving methotrexate, sulfasalazine or hydroxychloroquine (monotherapy or combination). Interventions: The intervention was disease-modifying anti-rheumatic drug cessation, followed by observation for 24 weeks or until flare, with clinical and immune monitoring. Outcome measures: The primary outcome measure was the proportion of participants experiencing a confirmed flare, defined as DAS28-CRP≥3.2 or DAS28-CRP≥2.4 twice within 2 weeks, and time to flare. Exploratory predictive modelling was also performed using multivariable Cox regression to understand risk factors for flare. Results: 121 participants were recruited between September 2018 and December 2020. Flare rate by week 24 was 52.3% (95% CI 43.0 to 61.7), with a median (IQR) time to flare of 63 (41-96) days. Female sex, baseline methotrexate use, anti-citrullinated peptide antibody level and rheumatoid factor level were associated with flare. An exploratory prediction model incorporating these variables allowed estimation of flare risk, with acceptable classification (C index 0.709) and good calibration performance. Conclusion: The rate of flare was approximately 50%. Several baseline clinical parameters were associated with flare. The BIO-FLARE study design provides a robust experimental medicine model for studying flare and remission immunobiology. Trial registration number: ISRCTN registry 16371380.
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Meeting report : The Systemic Lupus International Collaborating Clinics (SLICC) world Lupus seminar on AfricaThe 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.
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A review on the epidemiology of rheumatoid arthritis : an update and trends from current literatureRheumatoid arthritis (RA) is a systemic, chronic autoimmune disease affecting mainly the joints, often with extra articular manifestations. This review provides an update on RA epidemiological trends and management. PubMed and EMBASE were searched from 2014 to 2024 using rheumatoid arthritis as keyword, combined with incidence, prevalence, diagnosis, classification, and management. Emphasis was on papers published in the past 5 years. Globally, the age-standardised prevalence and incidence rate (ASPR and ASIR) of RA increased with varying figures. The ASPR increased by 0.37%, 14.1%, and 6.4% from 1990 to 2019, 2020 and 2017 respectively; and 9% from 1980 to 2019. The ASIR increased by 0.3% and 8.2% from 1990 to 2019 and 2017 respectively; the disability-adjusted life years (DALY) figures increased 0.12% and decreased 0.36% in the same period from different authors. Reduction in ASIR were reported while ASPR varies. Disease modifying anti-rheumatic drugs (DMARDs) remain the cornerstone of treatment.
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EXamining the feasibility of exerCisE to manage symptoms of Lupus (EXCEL) : a protocol for a randomised controlled pilot studyIntroduction: SLE is a chronic autoimmune disease that results in sustained hyperactivation of innate and adaptive immune cells and widespread inflammatory damage. Regular exercise reduces SLE symptoms including fatigue and joint pain and improves patient quality of life. However, most individuals with SLE are not sufficiently active to achieve these benefits, and guidance on the optimal approach to exercise is limited. EXCEL will examine the feasibility of conducting a large-scale randomised controlled trial comparing the effects of a remotely monitored, home-based, exercise programme with standard of care for individuals with SLE. Methods and analysis: 30 females with SLE will be recruited, and those randomised into Exercise (SLE-Ex) will codesign a progressive training plan with support from the research team. The aim of each 12-week plan will be to complete 150 min of moderate (60-70% heart rate max, HRmax) or 90 min of vigorous exercise (>70% HRmax) per week. SLE-Ex will be encouraged to exercise independently (without support) from weeks 13-18. Participants with SLE that are randomised into Control (SLE-Con) will maintain habitual activity without support for 18 weeks. Measures of feasibility and acceptability will be reported, and peripheral blood will be collected at weeks 0, 12 and 18 to explore whether the frequency, phenotype and metabolic profile of lymphocyte subsets has changed. Biomarkers of SLE activity, and self-reported measures of fatigue, sleep quality and health-related quality of life will also be monitored at these timepoints. Blood and self-reported measures will be compared with a healthy control (HC) group (n=15, age and body mass index matched) at baseline only. Ethics and dissemination: A favourable ethical opinion was given by South East Scotland Research Ethics Committee (22/SS/0082). Findings will be disseminated at conferences and published in peer-reviewed journals.
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Cutaneous vasculitis in systemic lupus erythematosus : epidemiology and risk factors over a 20-year follow-upObjectives: Cutaneous vasculitis (CV) is common in SLE, but the epidemiology and risk factors remain unclear. We aimed to identify the trends and risk factors for CV in patients with SLE over a period of 20 years. Methods: The Birmingham Lupus Cohort is an observational longitudinal cohort of SLE patients. Patients were enrolled within 3 years of meeting their fourth ACR criterion. Disease activity, laboratory test results and treatment records were collected. A multivariable shared frailty Cox proportional hazard model was used to identify clinical, laboratory, and treatment-related variables associated with the development of CV. Results: We included 392 patients: 92.5% were female. The median (IQR) duration of follow up was 9.2 (5.1-14.7) years. CV occurred in 27% of SLE patients, of whom 43.3% had two or more CV events. This study demonstrated a marked decline in the incidence rates of CV, decreasing from 34.4% (95% CI: 29.7, 39.3) during the first three years after enrolment to 2.1% (95% CI: 0.05, 11.5) after 18 years of follow-up. Development of CV was associated with Raynaud's phenomenon, constitutional, mucocutaneous, musculoskeletal, haematological, and cardiovascular involvement, anti-Sm antibodies, anti-dsDNA and hypocomplementemia. However, the use of azathioprine and antimalarials was inversely associated with the development of CV. Patients with CV were more likely to develop at least 1 item of organ damage. Conclusions: The incidence rates of CV in SLE decreased over the follow-up period and CV is associated with defined clinical, serological and treatment-related factors.
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Perceptions and experiences of individuals at-risk of rheumatoid arthritis (RA) knowing about their risk of developing RA and being offered preventive treatment: systematic review and thematic synthesis of qualitative studies.Objectives: There is increasing interest in identifying individuals at-risk of rheumatoid arthritis (RA) and initiating early treatment to prevent or delay the onset of arthritis. We aimed to describe the perceptions and experiences of at-risk individuals and to inform the conduct of clinical trials and studies, and clinical practice. Methods: A systematic review and thematic synthesis of qualitative studies was conducted. Two review authors independently screened studies for inclusion, appraised their methodological quality using the Critical Appraisal Skills Programme checklist and assessed confidence in the findings using the Grading of Recommendations Assessment, Development and Evaluation-Confidence in Evidence from Reviews of Qualitative Research approach. Results: Seven studies involving 115 individuals at-risk of developing RA were included. Three major themes (seven subthemes) were identified: understanding the risk of developing RA (knowledge of RA and identification of potential risk factors); preventive interventions to reduce the risk of developing RA (understanding the value and role of preventive interventions, and engagement with preventive interventions); and perceptions of predictive testing for RA (benefits of predictive testing, decision to undertake predictive testing and concerns about predictive testing). Moderate confidence in most review findings was evident. Conclusion: While there are clear benefits in informing individuals at-risk of RA about their risk following predictive testing and offering preventive treatment, there are potential barriers to engagement, intensified by the burden of uncertainty. Identification of the optimum approaches for presenting risk information, including the risks and benefits of engaging with preventive interventions, is urgently needed to support individuals at-risk of RA in their decision making.
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Prescribing anti-rheumatic drugs in pregnancy and breastfeeding-the British Society for Rheumatology guideline scope.Prescribing anti-rheumatic drugs in pregnancy and breastfeeding-the British Society for Rheumatology guideline scope
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Relationship between inflammation and metabolism in patients with newly presenting rheumatoid arthritisBackground: Systemic inflammation in rheumatoid arthritis (RA) is associated with metabolic changes. We used nuclear magnetic resonance (NMR) spectroscopy-based metabolomics to assess the relationship between an objective measure of systemic inflammation [C-reactive protein (CRP)] and both the serum and urinary metabolome in patients with newly presenting RA. Methods: Serum (n=126) and urine (n=83) samples were collected at initial presentation from disease modifying anti-rheumatic drug naïve RA patients for metabolomic profile assessment using 1-dimensional 1H-NMR spectroscopy. Metabolomics data were analysed using partial least square regression (PLS-R) and orthogonal projections to latent structure discriminant analysis (OPLS-DA) with cross validation. Results: Using PLS-R analysis, a relationship between the level of inflammation, as assessed by CRP, and the serum (p=0.001) and urinary (p<0.001) metabolome was detectable. Likewise, following categorisation of CRP into tertiles, patients in the lowest CRP tertile and the highest CRP tertile were statistically discriminated using OPLS-DA analysis of both serum (p=0.033) and urinary (p<0.001) metabolome. The most highly weighted metabolites for these models included glucose, amino acids, lactate, and citrate. These findings suggest increased glycolysis, perturbation in the citrate cycle, oxidative stress, protein catabolism and increased urea cycle activity are key characteristics of newly presenting RA patients with elevated CRP. Conclusions: This study consolidates our understanding of a previously identified relationship between serum metabolite profile and inflammation and provides novel evidence that there is a relationship between urinary metabolite profile and inflammation as measured by CRP. Identification of these metabolic perturbations provides insights into the pathogenesis of RA and may help in the identification of therapeutic targets.
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Rheumatoid arthritis prevention: any takers?Rheumatoid arthritis prevention: any takers?
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Rituximab 500 mg 6-monthly infusions is an option in maintenance therapy of ANCA-associated vasculitis.Rituximab 500 mg 6-monthly infusions is an option in maintenance therapy of ANCA-associated
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Spontaneously Resolving Joint Inflammation Is Characterised by Metabolic Agility of Fibroblast-Like Synoviocytes.Fibroblast-like synoviocytes (FLS) play an important role in maintaining joint homeostasis and orchestrating local inflammatory processes. When activated during injury or inflammation, FLS undergo transiently increased bioenergetic and biosynthetic demand. We aimed to identify metabolic changes which occur early in inflammatory disease pathogenesis which might support sustained cellular activation in persistent inflammation. We took primary human FLS from synovial biopsies of patients with very early rheumatoid arthritis (veRA) or resolving synovitis, and compared them with uninflamed control samples from the synovium of people without arthritis. Metabotypes were compared using NMR spectroscopy-based metabolomics and correlated with serum C-reactive protein levels. We measured glycolysis and oxidative phosphorylation by Seahorse analysis and assessed mitochondrial morphology by immunofluorescence. We demonstrate differences in FLS metabolism measurable after ex vivo culture, suggesting that disease-associated metabolic changes are long-lasting. We term this phenomenon 'metabolic memory'. We identify changes in cell metabolism after acute TNFα stimulation across disease groups. When compared to FLS from patients with early rheumatoid arthritis, FLS from patients with resolving synovitis have significantly elevated mitochondrial respiratory capacity in the resting state, and less fragmented mitochondrial morphology after TNFα treatment. Our findings indicate the potential to restore cell metabotypes by modulating mitochondrial function at sites of inflammation, with implications for treatment of RA and related inflammatory conditions in which fibroblasts play a role.
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Symptoms in first-degree relatives of patients with rheumatoid arthritis: evaluation of cross-sectional data from the symptoms in persons at risk of rheumatoid arthritis (SPARRA) questionnaire in the PRe-clinical EValuation of Novel Targets in RA (PREVeNT-RA) CohortBackground: First-degree relatives (FDRs) of people with rheumatoid arthritis (RA) have a fourfold increased risk of developing RA. The Symptoms in Persons At Risk of Rheumatoid Arthritis (SPARRA) questionnaire was developed to document symptoms in persons at risk of RA. The aims of this study were (1) to describe symptoms in a cohort of FDRs of patients with RA overall and stratified by seropositivity and elevated CRP and (2) to determine if patient characteristics were associated with symptoms suggestive of RA. Methods: A cross-sectional study of FDRs of patients with RA, in the PREVeNT-RA study, who completed a study questionnaire, provided a blood sample measured for rheumatoid factor, anti-CCP and CRP and completed the SPARRA questionnaire. Moderate/severe symptoms and symmetrical, small and large joint pain were identified and described. Symptoms associated with both seropositivity and elevated CRP were considered suggestive of RA. Logistic regression was used to determine if symptoms suggestive of RA were associated with patient characteristics. Results: Eight hundred seventy participants provided all data, 43 (5%) were seropositive and 122 (14%) had elevated CRP. The most frequently reported symptoms were sleep disturbances (20.3%) and joint pain (17.9%). Symmetrical and small joint pain were 11.3% and 12.8% higher, respectively, in those who were seropositive and 11.5% and 10.7% higher in those with elevated CRP. In the logistic regression model, seropositivity, older age and feeling depressed were associated with increased odds of small and symmetrical joint pain. Conclusions: This is the first time the SPARRA questionnaire has been applied in FDRs of patients with RA and has demonstrated that the presence of symmetrical and small joint pain in this group may be useful in identifying people at higher risk of developing RA.
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'It's just a great muddle when it comes to food': a qualitative exploration of patient decision-making around diet and gout.Objective: Our aim was to understand whether, why and how patients choose to modify their diets after developing gout. Methods: We conducted an inductive thematic secondary analysis of qualitative data from 43 interviews and four focus groups with UK participants with gout (n = 61). Results: Participants commonly initiated dietary changes as part of a self-management strategy for gout. Reasons for making such dietary changes included: desperation; a desire for control; and belief that it would be possible to achieve successful management through diet alone; but not weight loss. Participants who did not make changes or who reverted to previous dietary patterns did so because: they believed urate-lowering therapy was successfully managing their gout; medication allowed normal eating; they did not find 'proof' that diet would be an effective treatment; or the dietary advice they found was unrealistic, unmanageable or irrelevant. Dietary modification was patient led, but patients would have preferred the support of a health-care professional. Beliefs that diet could potentially explain and modify the timing of flares gave patients a sense of control over the condition. However, the belief that gout could be controlled through dietary modification appeared to be a barrier to acceptance of management with urate-lowering therapy. Conclusions: Perceptions about gout and diet play a large role in the way patients make decisions about how to manage gout in their everyday lives. Addressing the reasons why patients explore dietary solutions, promoting the value of urate-lowering therapy and weight loss and drawing on strong evidence to communicate clearly will be crucial in improving long-term clinical management and patient experience.
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Intimate Partner Violence and the Risk of Developing Fibromyalgia and Chronic Fatigue Syndrome.Intimate partner violence (IPV) is a global public health issue with a variety of ill health consequences associated with exposure. Due to the stimulation of chronic stress and inflammatory pathways, childhood abuse has been associated with the subsequent development of functional syndromes such as fibromyalgia and chronic fatigue syndrome (CFS). Although IPV in women appears to elicit similar biochemical responses, this association has not been tested thoroughly in IPV survivors. These functional syndromes are complex in etiology and any indication of their risk factors would benefit health care professionals managing this population. Therefore, we aimed to investigate the association between exposure to IPV with functional syndromes: fibromyalgia and CFS. We conducted a retrospective open cohort study using "The Heath Improvement Network" database between January 1, 1995 and December 1, 2017. A total of 18,547 women who were exposed to IPV were each matched by age to four controls who were not exposed (n = 74,188). The main outcome measures were the risk of developing fibromyalgia and CFS. These were presented as adjusted incidence rate ratios (aIRR) with 95% confidence intervals (CIs). We found that 97 women in the exposed group developed fibromyalgia (incidence rate [IR] = 1.63 per 1,000 person-years) compared to 239 women in the unexposed group (IR = 0.83 per 1,000 person-years). Following adjustment, this translated to an IRR of 1.73 (95% CI = [1.36, 2.22]). Similarly, 19 women developed CFS in the exposed group (IR = 0.32 per 1,000 person-years), compared to 53 in the unexposed group (0.18 per 1,000 person-years), which translates to an aIRR of 1.92 (95% CI = [1.11, 3.33]). Therefore, we have identified an association between a history of IPV in women and the development of these functional syndromes, which may provide more information to inform the biopsychosocial pathway precipitating the development of fibromyalgia and CFS.
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Management of bone health in idiopathic inflammatory myopathies : a two-center audit in the United Kingdom and Hong KongBackground: Patients with inflammatory idiopathic myopathies (IIM) face elevated risks of osteoporosis and fragility fracture. Aim: To evaluate current practice relating to bone health in adult patients with IIM in the United Kingdom and Hong Kong (HK). Methods: Patients were identified from IIM patient lists. Demographics, osteoporosis risk factors, DXA scans, and bone protection treatment were recorded. Adherence to regional standards was evaluated for each center. Following this, in the United Kingdom, up-to-date DXA scans were performed. Results: Of 136 patients identified, 51 met selection criteria (UK, n = 20, HK, n = 31). Mean age in the United Kingdom was 59 (IQR 54-66); in Hong Kong, 65 (IQR 52.5-70). Most were female (UK 70%; HK 77%), current or previous steroid treatment was common (UK 90%; HK 100%) and some had experienced fragility fracture (UK 15%; HK 9%). The mean daily dose of prednisolone that patients were prescribed during the study was 12.5 mg (UK) and 14.3 mg (HK). Some patients had had a DXA scan (UK 50%; HK 35%) though several were outdated. Among those with BMD measured (UK, n = 20; HK, n = 11), osteopenia prevalence was 35% (UK) and 36% (HK) while osteoporosis was 5% (UK) and 36% (HK). Notably, 25% (UK) and 64% (HK) exceeded treatment thresholds. Treatments included anti-osteoporotic agents (UK 55%; HK 15%), Vitamin D/calcium supplements (UK 95%; HK 52%), or no treatment (UK 5%, HK 15%). Conclusion: Poor compliance with guidelines exists in both centers, particularly around investigation and monitoring of bone health for IIM patients. Integrated care models and increased resource allocation to bone health are imperative to improve management of this aspect of IIM.
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Understanding the impact of systemic lupus erythematosus on work amongst South Asian people in the UK: An explorative qualitative studySLE has a range of fluctuating symptoms affecting individuals and their ability to work. Although South Asian (SA) patients are at increased risk of developing SLE there is limited knowledge of the impact on employment for these patients in the UK. Understanding ethnicity and disease-specific issues are important to ensure patients are adequately supported at work. Semi-structured interviews were conducted with patients of SA origin to explore how SLE impacted on their employment. Thematic analysis was used to analyse the data which are reported following COREQ guidelines. Ten patients (8 female; 2 male) were recruited from three rheumatology centres in the UK and interviewed between November 2019 and March 2020. Patients were from Indian (n = 8) or Pakistani (n = 2) origin and worked in a range of employment sectors. Four themes emerged from the data: (1) Disease related factors; (2) Employment related factors; (3) Cultural and interpersonal factors impacting on work ability; (4) Recommendations for improvement. Patients' ability to work was affected by variable work-related support from their hospital clinicians, low awareness of SLE and variable support from their employers, and cultural barriers in their communities that could affect levels of family support received. These findings highlight the need for additional support for SA patients with SLE in the workplace.
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Impact of glucocorticoids on the incidence of lupus-related major organ damage: a systematic literature review and meta-regression analysis of longitudinal observational studies.Objective: In systemic lupus erythematosus (SLE), disease activity and glucocorticoid (GC) exposure are known to contribute to irreversible organ damage. We aimed to examine the association between GC exposure and organ damage occurrence. Methods: We conducted a literature search (PubMed (Medline), Embase and Cochrane January 1966-October 2021). We identified original longitudinal observational studies reporting GC exposure as the proportion of users and/or GC use with dose information as well as the occurrence of new major organ damage as defined in the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Meta-regression analyses were performed. Reviews, case-reports and studies with <5 years of follow-up, <50 patients, different outcomes and special populations were excluded. Results: We selected 49 articles including 16 224 patients, 14 755 (90.9%) female with a mean age and disease duration of 35.1 years and of 37.1 months. The mean follow-up time was 104.9 months. For individual damage items, the average daily GC dose was associated with the occurrence of overall cardiovascular events and with osteoporosis with fractures. A higher average cumulative dose adjusted (or not)/number of follow-up years and a higher proportion of patients on GC were associated with the occurrence of osteonecrosis. Conclusions: We confirm associations of GC use with three specific damage items. In treating patients with SLE, our aim should be to maximise the efficacy of GC and to minimise their harms.