Validity and sensitivity to change of laser Doppler imaging as a novel objective outcome measure for cutaneous lupus erythematosus.

OBJECTIVES: The objectives of this study were to assess the reliability of a novel objective outcome measure, laser Doppler imaging (LDI), its validity against skin biopsy histology and other clinical instruments, including localized cutaneous lupus disease area and severity index (L-CLASI) and visual analogue scale (VAS) score of photographs, and its responsiveness to clinical change with therapy. METHODS: A prospective observational cohort study was conducted in 30 patients with active cutaneous lupus erythematosus (CLE). At baseline and 3 months, disease activity was assessed using L-CLASI and a high resolution LDI system by two assessors. Skin biopsy was scored as 0 = non-active, 1 = mild activity and 2 = active. Photographs were assessed by two clinicians using 100 mm VAS. Inter-rater reliability was analyzed using Bland-Altman limits of agreement. Correlation between histology and LDI, L-CLASI and VAS and sensitivity to change of LDI with physician subjective assessment of change (PSAC) at 3 months were analyzed using Kendall's tau-a. RESULTS: Of 30 patients with CLE, 28 (93%) were female, mean (SD) age 48.4 (11.5) y, 25 (83%) were Caucasians, 25 (83%) had concurrent systemic lupus erythematosus and 16 (53%) were smokers. CLE subtypes were acute = 9, subacute = 8 and chronic = 13. Inter-rater agreement for LDI was fair but for VAS score of photographs was poor. In 20 patients with biopsy, correlation with histology was better for LDI (tau-a = 0.53) than L-CLASI (tau-a = 0.26) (difference = 0.27; 90% CI 0.05-0.49) or VAS score of photographs (tau-a = 0.17) (difference = 0.36; 90% CI 0.04-0.68). There was a moderate correlation between PSAC score and change in LDI (tau-a = 0.56; 90% CI 0.38-0.74; p < 0.001, n = 15). CONCLUSION: LDI provides a reliable, valid and responsive quantitative measure of inflammation in CLE. It has a better correlation with histology compared to clinical instruments. LDI provides an objective outcome measure for clinical trials.

Work participation, mobility and foot symptoms in people with systemic lupus erythematosus: findings of a UK national survey.

OBJECTIVE: The aim of this study was to investigate whether foot and lower limb related symptoms were associated with work participation and poor mobility in people with Systemic Lupus Erythematosus (SLE). METHOD: A quantitative, cross-sectional, self-reported survey design was utilised. People with SLE from six United Kingdom (UK) treatment centres and a national register were invited to complete a survey about lower limb and foot health, work participation and mobility. Data collected included work status and the prevalence of foot symptoms. The focus of the analyses was to explore potential associations between poor foot health work non-participation. RESULTS: In total, 182 useable surveys were returned. Seventy-nine respondents reported themselves as employed and 32 reported work non-participation. The remaining were retired due to age or reported work non-participation for other reasons. Work non-participation due to foot symptoms was significantly associated with difficulty walking (p = 0.024), past episodes of foot swelling (p = 0.041), and past episodes of foot ulceration (p = 0.018). There was a significant increase in foot disability scores amongst those not working (mean 18.13, 95% CI: 14.85-21.41) compared to those employed (mean 10.16, 95% CI: 8.11-12.21). CONCLUSIONS: Twenty-nine% of people with SLE reported work non-participation because of lower limb or foot problems. Our results suggest that foot health and mobility may be important contributors to a persons' ability to remain in work and should be considered as part of a clinical assessment.

Publisher Correction: A novel two-score system for interferon status segregates autoimmune diseases and correlates with clinical features.

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A novel two-score system for interferon status segregates autoimmune diseases and correlates with clinical features.

Measurement of type I interferon (IFN-I) has potential to diagnose and stratify autoimmune diseases, but existing results have been inconsistent. Interferon-stimulated-gene (ISG) based methods may be affected by the modularity of the ISG transcriptome, cell-specific expression, response to IFN-subtypes and bimodality of expression. We developed and clinically validated a 2-score system (IFN-Score-A and -B) using Factor Analysis of 31 ISGs measured by TaqMan selected from 3-IFN-annotated modules. We evaluated these scores using in-vitro IFN stimulation as well as in sorted cells then clinically validated in a cohort of 328 autoimmune disease patients and healthy controls. ISGs varied in response to IFN-subtypes and both scores varied between cell subsets. IFN-Score-A differentiated Systemic Lupus Erythematosus (SLE) from both Rheumatoid Arthritis (RA) and Healthy Controls (HC) (both p < 0.001), while IFN-Score-B differentiated SLE and RA from HC (both p < 0.001). In SLE, both scores were associated with cutaneous and hematological (all p < 0.05) but not musculoskeletal disease activity. Comparing with bimodal (IFN-high/low) classification, significant differences in IFN-scores were found between diagnostic groups within the IFN-high group. Our continuous 2-score system is more clinically relevant than a simple bimodal classification of IFN status. This system should allow improvement in diagnosis, stratification, and therapy in IFN-mediated autoimmunity.

Patients' experiences of lupus-related foot problems: a qualitative investigation.

Background Systemic lupus erythematosus (SLE) can present with a variety of symptoms. Previous research has shown there is a high prevalence of lower limb and foot problems in patients with SLE associated with the musculoskeletal, vascular and neurological changes. Furthermore, there is a high prevalence of infections affecting the feet and a range of common skin and nail problems. However, it is not known how these foot problems impact upon people's lives. Therefore, we aimed to explore this using a qualitative approach. Method Following ethical approval, 12 participants were recruited who had a diagnosis of SLE, current and/or past experience of foot problems and were over 18 years in age. Following consent, interviews were carried out with an interpretivist phenomenological approach to both data collection and analysis. Results Seven themes provide insight into: foot problems and symptoms; the impact of these foot problems and symptoms on activities; disclosure and diagnosis of foot problems; treatment of foot problems and symptoms; perceived barriers to professional footcare; unanswered questions about feet and footcare; and identification of the need for professional footcare and footcare advice. Conclusion These participants tend to "self-treat" rather than disclose that they may need professional footcare. A lack of focus upon foot health within a medical consultation is attributed to the participant's belief that it is not within the doctor's role, even though it is noted to contribute to reduced daily activity. There is a need for feet to be included as a part of patient monitoring and for foot health management to be made accessible for people with SLE.

The prevalence of self-reported lower limb and foot health problems experienced by participants with systemic lupus erythematosus: Results of a UK national survey.

Objective The main aim of this survey was to determine the frequency of self-reported lower limb or foot and ankle complications experienced by participants with systemic lupus erythematosus (SLE). A secondary aim was to determine the frequency of treatments that have been received or that participants with SLE may like to receive if offered. Method A quantitative, cross-sectional, self-reported survey design was utilized. The developed survey was checked for face and content validity prior to patient partner cognitive debriefing in order to ensure usability, understanding of the process of completion and of the questions posed. The full protocol for survey development has been published previously. Results This is the first comprehensive national UK survey of lower limb and foot health problems reported by participants with SLE. A high prevalence of vascular, dermatological and musculoskeletal complications was reported by survey respondents. Additionally, whilst the relative prevalence of sensory loss was low, a quarter of people reported having had a fall related to changes in foot sensation demonstrating a previously unknown rate and cause of falls. Conclusion Complications related to vascular, dermatological and musculoskeletal health are identified as particularly prevalent in participants with SLE. Further, there is a suggestion that the provision of interventions to maintain lower limb health is highly varied and lacks national standardization, despite there being a strong indication of participant reported need. The findings of this work can be used to inform care guideline development in addition to identifying areas for future research.

Management of nonresponse to rituximab in rheumatoid arthritis: predictors and outcome of re-treatment.

OBJECTIVE: A proportion of patients with rheumatoid arthritis (RA) have disease that fails to respond to an initial cycle of rituximab. Using highly sensitive flow cytometry (HSFC), it has been shown that most patients who do not exhibit a response, as measured using the European League Against Rheumatism (EULAR) criteria, have persistent circulating B cell levels at week 2 after initial treatment with rituximab. This study was undertaken to examine whether an additional cycle of rituximab would improve B cell depletion and clinical response in patients whose disease did not respond to the initial cycle. METHODS: Patients with RA (n = 158) were treated with a first cycle of rituximab (2 infusions of 1 gm each). Clinical responses were assessed using EULAR criteria, and patients were categorized as either first-cycle responders or first-cycle nonresponders. Baseline characteristics of first-cycle nonresponders (n = 38) and first-cycle responders (n = 65) with complete data were compared. First-cycle nonresponders (n = 25) were treated with a second cycle of rituximab at least 6 months after the first cycle. HSFC was performed at baseline, immediately prior to the second infusion (week 2), 1 month after the second infusion (week 6), and then every 3 months for each cycle of rituximab. Complete B cell depletion was defined as being <0.0001 x 10(9) cells/liter. RESULTS: At baseline, the number of preplasma cells was significantly higher in first-cycle nonresponders than in first-cycle responders (P = 0.003). Following the first infusion of the first cycle of rituximab, only 9% of first-cycle nonresponders (3 of 34) exhibited complete depletion of B-lineage cells, compared with 37% of first-cycle responders (22 of 59) (P = 0.007). Following the first infusion of the second cycle of rituximab, 38% of first-cycle nonresponders exhibited complete depletion. Twenty-six weeks after the second cycle, there was a significant improvement in the Disease Activity Score in 28 joints, with 72% of patients exhibiting a EULAR response. CONCLUSION: RA patients whose disease did not respond to an initial cycle of rituximab have higher circulating preplasma cell numbers at baseline and incomplete depletion. Our findings indicate that an additional cycle of rituximab administered prior to total B cell repopulation enhances B cell depletion and clinical responses.

Reduction of fatigue in Sjögren syndrome with rituximab: results of a randomised, double-blind, placebo-controlled pilot study.

OBJECTIVE: Primary Sjögren syndrome (pSS) causes significant systemic symptoms including fatigue as well as glandular dysfunction. There are currently no effective systemic therapies; however, open label series have suggested that rituximab may be beneficial for systemic and glandular manifestations. Therefore, we performed a double blind, placebo-controlled, randomised pilot study of the efficacy of rituximab in reducing fatigue in pSS. METHODS: A total of 17 patients with pSS and a score on fatigue visual analogue scale (VAS) >50 were randomised to receive either 2 infusions of rituximab 1 g or placebo; patients also received oral and intravenous steroids. Outcome measures included: the proportion of patients with >20% reduction in fatigue VAS, changes in pSS related symptoms, health related quality of life and immunological parameters of pSS. These were measured 6 months after therapy. RESULTS: There was significant improvement from baseline in fatigue VAS in the rituximab group (p<0.001) in contrast to the placebo group (p = 0.147). There was a significant difference between the groups at 6 months in the social functioning score of SF-36 (p = 0.01) and a trend to significant difference in the mental health domain score of SF-36 (p = 0.06). There was one episode of serum sickness in the rituximab treated group. CONCLUSIONS: This is the first double blind study of rituximab in pSS to show benefit; further studies are justified.

Premature osteoarthritis of the knee associated with cartilage hypertrophy and phalangeal dysgenesis.

A woman presented with premature knee osteoarthritis associated with marked femoral cartilage hypertrophy. She also exhibited phalangeal dysgenesis, suggesting this may be an unrecognised syndrome that may predispose to knee osteoarthritis.