Mycophenolate mofetil in the treatment of lupus nephritis

Lupus nephritis is a complication of systemic lupus erythematosus, which has significant morbidity and mortality. The accepted standard of treatment for severe lupus nephritis is cyclophosphamide for induction of remission. This has significant adverse effects including severe infection and amenorrhea. In addition, although cyclophosphamide induces remission, long-term mortality does not seem to be altered. Mycophenolate mofetil (MMF) is an immunosuppressive agent originally used in solid organ transplantation, which has been compared with cyclophosphamide in trials for lupus nephritis. Randomized trials with MMF have been relatively small, although pooled data seem to suggest that it is at least as effective as cyclophosphamide in inducing remission. In addition, MMF has also been associated with a reduced risk of infection and amenorrhea, although this finding is not universal. MMF appears to be associated with more diarrhea compared with cyclophosphamide. MMF is likely to be a useful treatment for lupus nephritis, although available trial data are limited due to the small size of previous studies. A large trial (the Aspreva Lupus Management Study) is currently underway to attempt to establish the place of MMF in treatment of lupus nephritis

Is it me? The impact of patient-physician interactions on lupus patients' psychological well-being, cognition and health-care-seeking behaviour

Objective. The aim was to explore the impact of patient-physician interactions, pre- and postdiagnosis, on lupus and UCTD patients' psychological well-being, cognition and health-care-seeking behaviour. Methods. Participants were purposively sampled from the 233 responses to a survey on patient experiences of medical support. Twenty-one semi-structured interviews were conducted and themes generated using thematic analysis. Results. The study identified six principal themes: (i) the impact of the diagnostic journey; (ii) the influence of key physician(s) on patient trust and security, with most participants reporting at least one positive medical relationship; (iii) disparities in patient-physician priorities, with patients desiring more support with quality-of-life concerns; (iv) persisting insecurity and distrust, which was prevalent and largely influenced by previous and anticipated disproportionate (often perceived as dismissive) physician responses to symptoms and experiences of widespread inadequate physician knowledge of systemic autoimmune diseases; (v) changes to health-care-seeking behaviours, such as curtailing help-seeking or under-reporting symptoms; and (vi) empowerment, including shared medical decisionmaking and knowledge acquisition, which can mitigate insecurity and improve care. Conclusion. Negative medical interactions pre- and post-diagnosis can cause a loss of selfconfidence and a loss of confidence and trust in the medical profession. This insecurity can persist even in subsequent positive medical relationships and should be addressed. Key physicians implementing empowering and security-inducing strategies, including being available in times of health crises and validating patient-reported symptoms, might lead to more trusting medical relationships and positive health-care-seeking behaviour

Development of antigen-specific ELISA for circulating autoantibodies to extracellular matrix protein 1 in lichen sclerosus

Lichen sclerosus is a common, acquired chronic inflammatory skin disease of unknown etiology, although circulating autoantibodies to the glycoprotein extracellular matrix protein 1 (ECM1) have been detected in most patients’ sera. We have examined the nature of ECM1 epitopes in lichen sclerosus sera, developed an ELISA system for serologic diagnosis, and assessed clinicopathological correlation between ELISA titer and disease. Epitope-mapping studies revealed that lichen sclerosus sera most frequently recognized the distal second tandem repeat domain and carboxyl-terminus of ECM1. We analyzed serum autoantibody reactivity against this immunodominant epitope in 413 individuals (95 subjects with lichen sclerosus, 161 normal control subjects, and 157 subjects with other autoimmune basement membrane or sclerosing diseases). The ELISA assay was highly sensitive; 76 of 95 lichen sclerosus patients (80.0%) exhibited IgG reactivity. It was also highly specific (93.7%) in discriminating between lichen sclerosus and other disease/control sera. Higher anti-ECM1 titers also correlated with more longstanding and refractory disease and cases complicated by squamous cell carcinoma. Furthermore, passive transfer of affinity-purified patient IgG reproduced some histologic and immunopathologic features of lichen sclerosus skin. This new ELISA is valuable for the accurate detection and quantification of anti-ECM1 autoantibodies. Moreover, the values may have clinical significance in patients with lichen sclerosus

Medication decision-making and adherence in lupus: Patient-physician discordance and the impact of previous ‘Adverse Medical Experiences’

OBJECTIVES: Medication adherence is critical in the successful management of lupus. There is very limited existing literature on reasons why non-adherence is not reported. This study explores the impact of current and previous medical experiences on patient satisfaction, adherence and reporting of non-adherence. METHODS: Mixed methodology involved thematic analysis of in-depth interviews (n = 23) to further explore the statistically analysed quantitative survey findings (n = 186). RESULTS: This study identified five themes: (i) physician-patient discordance and a 'hierarchy of evidence' in medication decisions; (ii) the association of adherence with satisfaction with care; (iii) the persisting impact of past adverse medical experiences (AMEs); (iv) the dynamic balance of patient-physician control; and (v) holistic care, beyond a purely medication-based focus. Improving quality of life (43% of participants) and a supportive medical relationship (24%) were the main reasons for adherence. Patient-priorities and self-reported symptoms were perceived as less important to physicians than organ-protection and blood results. Non-reporters of non-adherence, non-adherers and those with past AMEs (e.g. psychosomatic misdiagnoses) had statistically significant lower satisfaction with care. The importance of listening to patients was a key component of every theme, and associated with patient satisfaction and adherence. The mean rating for rheumatologist's listening skills was 2.88 for non-adherers compared with 3.53 for other participants (mean difference 0.65, P = 0.003). CONCLUSION: Patients would like more weight and discussion given to self-reported symptoms and quality of life in medication decisions. Greater understanding and interventions are required to alleviate the persisting impact of past AMEs on some patients' wellbeing, behaviour and current medical relationships

Numerical scoring for the BILAG-2004 index

Objective. To develop an additive numerical scoring scheme for the BILAG-2004 index

The BILAG-2004 systems tally-a novel way of representing the BILAG-2004 index scores longitudinally

Objective. This was an exploratory analysis to develop a new way of representing BILAG-2004 system scores longitudinally that would be clinically meaningful and easier to analyse in comparison with multiple categorical variables. Methods. Data from a multicentre longitudinal study of SLE patients (the BILAG-2004 index and therapy collected at every visit) were used. External responsiveness analysis of the index suggested the possibility of using counts of systems with specified transitions in scores as a basis to analyse the system scores. Exploratory analyses with multinomial logistic regression were used to examine the appropriateness of this new method of analysing BILAG-2004 system scores. Receiver operating characteristic (ROC) curve analysis was used to assess the performance of this approach. Results. There were 1414 observations from 347 patients. A novel method was devised based on counts of systems with defined transitions in score (BILAG-2004 systems tally, BST). It has six components (systems with major deterioration, systems with minor deterioration, systems with persistent significant activity, systems with major improvement, systems with minor improvement and systems with persistent minimal or no activity). This was further simplified (simplified BST, sBST) into three components (systems with active/worsening disease, systems with improving disease and systems with persistent minimal or no activity). Both versions had expected associations with change in therapy. ROC curve analyses demonstrated that both versions had similar good performance characteristics (areas under the curve >0.80) in predicting increase in therapy. Conclusion. The BST and sBST provide alternative approaches to representing BILAG-2004 disease activity longitudinally. Further validation of their use is required

‘But you don’t look sick’: a qualitative analysis of the LUPUS UK online forum

Funder: University of CambridgeAbstract: Lupus is a multi-system autoimmune rheumatic disease with increased morbidity and mortality. Some manifestations are life-threatening with many aspects of living with the disease, difficulties in diagnosis and accessing appropriate medical care, having an impact on quality of life. The disease itself, and these patients’ perspectives, are currently poorly understood and under-researched. The LUPUS UK forum of conversations between over 25,000 members provides a rich environment to explore the views of these patients. Conversations on the LUPUS UK online forum were qualitatively explored using virtual ethnography and thematic analysis. The forum itself and positive medical relationships were widely considered to provide a means of support, understanding and validation. Forum members expressed difficulties in diagnosis, disease management, and the psychological and physical impact of living with an unpredictable, poorly understood disease, often with life-changing symptoms. Invalidating personal, social and medical environments were perceived as exacerbating these difficulties. Delays in diagnosis and misdiagnoses were frequently discussed as causing significant damage, especially when symptoms were disbelieved or dismissed. Invalidation was the key theme with further themes of: Uncertainty, Medical (mis)communications and misunderstandings, Navigating health systems and Resilience and support. Although effective care and support was reported by some members, the negative impact of living with an incurable, life-changing disease was often exacerbated by perceived invalidation, uncertainty, and difficulties in multiple areas of members’ lives. Improved knowledge of the disease and greater support at all stages of the diagnostic journey could improve outcomes and quality of life for these patients