Body image mediates the impact of pain on depressive symptoms in patients with systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with treatment manifestations that can cause changes in appearance, including skin rashes, alopecia, vitiligo, and scars. SLE has been shown to adversely impact body image outcomes, and previous research has identified that greater disease activity is associated with worse body image outcomes which, in turn, are associated with greater depressive symptoms. For patients with SLE who also experience significant pain, poor body image outcomes may further compromise wellbeing and lead to greater depressive symptoms. The role of pain in body image has not been explored in SLE. Thus, the present study examined whether body image (specifically, body image-related quality of life) serves as a mediator of the relationship between pain and depressive symptoms among patients with SLE. METHODS: Multiple mediation analysis was used to examine the hypothesis that body image-related quality of life mediates the relationship between pain and depressive symptoms in a sample of patients with SLE (N = 135) from an urban region in Los Angeles, California. RESULTS: The sample was predominately female (92.6%) with a mean disease duration of approximately 17 years. Approximately one-quarter of the sample had elevated depressive symptoms. Body image-related quality of life was a significant mediator in the relationship between pain and depressive symptoms. The model accounted for 51% of the total variance in depressive symptoms (R2 = 0.51). CONCLUSION: This cross-sectional study suggested that body image-related quality of life may mediate the effects of pain on depressive symptoms among patients with SLE.

Screening characteristics for enrichment of individuals at higher risk for transitioning to classified SLE.

OBJECTIVE: Further prospective study is needed to elucidate the etiology and natural history of systemic lupus erythematosus development. The clinical complexity of this heterogeneous disease makes study design challenging. Our objective was to ascertain useful screening factors for identifying at-risk individuals for follow-up rheumatologic assessment or inclusion in prospective studies. METHODS: We attempted to re-contact 3823 subjects with a family history of systemic lupus erythematosus, who did not meet American College of Rheumatology systemic lupus erythematosus classification at a baseline study visit; 436 agreed to follow-up participation an average of 6.3 years after baseline. In total, 56 of these individuals had transitioned to classified systemic lupus erythematosus (≥ 4 cumulative American College of Rheumatology criteria, verified by medical record review) by the time of follow up. Generalized estimating equations assessed associations between our dichotomous outcome of transitioning to systemic lupus erythematosus with baseline characteristics, including ANA positivity, Connective Tissue Disease Screening questionnaire systemic lupus erythematosus score, and number of American College of Rheumatology criteria. We analyzed predictive accuracy of characteristics on transitioning. RESULTS: ANA positivity, Connective Tissue Disease Screening questionnaire systemic lupus erythematosus score categorization of possible or probable systemic lupus erythematosus, and greater number of American College of Rheumatology criteria at baseline were each associated with transitioning to systemic lupus erythematosus classification. Being ANA positive and having confirmed immunologic criteria at baseline had the highest positive predictive value and specificity for transitioning to systemic lupus erythematosus. American College of Rheumatology Connective Tissue Disease Screening questionnaire systemic lupus erythematosus score categorization of possible or probable systemic lupus erythematosus had a better positive predictive value, negative predictive value, sensitivity, and specificity than ANA positivity. CONCLUSION: Given limited resources, identifying individuals for follow up based on the systemic lupus erythematosus portion of the Connective Tissue Disease Screening questionnaire could be an efficient way to identify family members at highest risk of disease transition.

Psychometric validation of the Arthritis Helplessness Index in systemic lupus erythematosus.

Objective Helplessness is a relevant construct in systemic lupus erythematosus (SLE), an unpredictable chronic illness with no known cure characterized by relapsing and remitting features. However, no measure of helplessness has been validated in this population. The present study examined the structural validity, reliability, and convergent validity of the Arthritis Helplessness Index, a measure initially developed for rheumatoid arthritis populations, in a sample of patients with SLE. Methods Patients with SLE ( N = 136) receiving medical care at a private hospital completed the Arthritis Helplessness Index and other self-report measures. The structural validity of the Arthritis Helplessness Index was examined using confirmatory factor analysis. Internal consistency reliability was evaluated with Cronbach's coefficient alpha. Pearson product-moment correlations were used to examine convergent validity with measures of depression, anxiety and mastery. Results The five-item Arthritis Helplessness Index-Helplessness measure demonstrated a tenable factor structure (comparative fit index 0.98, root mean square error of approximation 0.06, standardized root mean residual 0.04). Internal consistency reliability was fair (α = 0.69). Convergent validity was evidenced by significant correlations with measures of depression, anxiety and mastery. Conclusion The five-item Arthritis Helplessness Index-Helplessness scale can confidently be used as a measure of helplessness in SLE.

Decreased amplitude of surface electromyo- graphic recordings of muscle activation along the posterior myofascial kinematic chain in subjects with chronic nonspecific low back pain compared to healthy subjects.

BACKGROUND: The concept of myofascial continuity suggests that muscles activate along kinematic chains with common fascial coverings. Yet, the literature lacks evidence in regards to the function of anatomical chains in populations suffering from low back pain (LBP). OBJECTIVE: To examine muscle activations along the superficial back line in LBP patients compared to healthy controls. METHODS: The sample study included 20 males with chronic LBP (mean age 28.7 (± 3.05) years, mean BMI 24.91 (± 2.76)) and 17 healthy controls (mean age 31.06 (± 7.76) years, mean BMI 23.46 (± 3.43)). Muscle activation (gastrocnemius, hamstrings, erector spine, and upper trapezius) along the superficial back line was measured using surface EMG. All subjects underwent five test conditions: Conditions 1-3 involved passive movement, active movement and active movement against maximum isometric resistance of the right gastrocnemius muscle. Conditions 4 and 5 involved neck extension without and with isometric resistance from the prone position. The main outcome was relative muscle activation amplitude between research and control subjects. RESULTS: Muscle activation along the posterior anatomical chain was observed during distal movement (plantar flexion or neck extension). LBP patients showed significant lower muscle activation in the erector spine of lower back region compared with the control group during active plantar flexion and active neck extension (p< 0.05). Lower muscle activation in other regions (gastrocnemius, hamstrings, erector spine level T6) was observed in the research group (although not significant). CONCLUSION: LBP may cause or result in a lower muscle activation of the posterior kinematic myofascial chain muscles.

Less than 7 hours of sleep per night is associated with transitioning to systemic lupus erythematosus.

Background The role of sleep in the etiology of systemic lupus erythematosus (SLE) has not been well studied. We examined whether sleep duration was associated with subsequent transitioning to SLE in individuals at risk for SLE. Methods Four hundred and thirty-six relatives of SLE patients who did not have SLE themselves at baseline were evaluated again an average of 6.3 (± 3.9) years later. Fifty-six individuals transitioned to SLE (≥ 4 cumulative American College of Rheumatology (ACR) criteria). Sleep duration, medication use and medical history were assessed by questionnaire; ACR criteria were confirmed by medical record review. Vitamin D was measured by ELISA. Generalized estimating equations, accounting for correlation within families, assessed associations between baseline sleep and the outcome of transitioning to SLE. Results Reporting sleeping less than 7 hours per night at baseline was more common in those who subsequently transitioned than those who did not transition to SLE (55% versus 32%, p = 0.0005; OR: 2.8, 95% CI 1.6-4.9). Those who transitioned to SLE were more likely to sleep less than 7 hours per night than those who did not transition to SLE adjusting for age, sex and race (OR: 2.8, 95% CI 1.6-5.1). This association remained after individual adjustment for conditions and early symptoms that could affect sleep, including prednisone use, vitamin D deficiency and number of ACR criteria (OR: 2.0, 95% CI 1.1-4.2). Conclusion Lack of sleep may be associated with transitioning to SLE, independent of early clinical manifestations of SLE that may influence sleep duration. Further evaluation of sleeping patterns and biomarkers in at-risk individuals is warranted.

The psychometric properties of the Perceived Stress Scale-10 among patients with systemic lupus erythematosus.

Objective Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disease characterized by periods of remission and recurrent flares, which have been associated with stress. Despite the significance of stress in this disease, the Perceived Stress Scale-10 has yet to be psychometrically evaluated in patients with SLE. Methods Exploratory factor analysis was used to examine the structural validity of the Perceived Stress Scale-10 among patients with SLE ( N = 138) receiving medical care at Cedars Sinai Medical Center. Cronbach's coefficient alpha was used to examine internal consistency reliability, and Pearson product-moment correlations were used to examine convergent validity with measures of anxiety, depression, helplessness, and disease activity. Results Exploratory factor analysis provided support for a two-factor structure (comparative fit index = .95; standardized root mean residual = .04; root mean square error of approximation = .08). Internal consistency reliability was good for both factors (α = .84 and .86). Convergent validity was evidenced via significant correlations with measures of anxiety, depression, and helplessness. There were no significant correlations with the measure of disease activity. Conclusion The Perceived Stress Scale-10 can be used to examine perceived stress among patients with SLE.

Failure of a systemic lupus erythematosus response index developed from clinical trial data: lessons examined and learned.

Background Our primary goal was to create an outcome change score index similar to a standard rheumatoid arthritis (RA) model utilizing real-world data in systemic lupus erythematosus (SLE) patients that occurred during their phase 3 trials with a Food and Drug Administration-approved drug. Methods We utilized raw data from trials of belimumab for the treatment of SLE. Data were split 80/20 into training/validation sets. Index variables present in a majority of patients and with face validity were selected. Variables were scored for each patient as percentage improvement from baseline after one year. The percentage of placebo- and drug-treated patients considered improved after the application of various criteria was ascertained. Logistic regression was employed to determine the ability of the new index to predict treatment assignment. Results A total of 1693 subjects had data for analyses. Eight variables were chosen: arthritis, rash, physician global assessment, fatigue, anti-double stranded DNA antibodies, C3, C4 and C-reactive protein. In the training dataset, ≥20% improvement in ≥4 of eight variables produced the largest difference between placebo- and drug-treated patients (22.1%) with an acceptable rate of improved placebo-treated patients (25%). This resulted in an odds ratio for belimumab (10 mg/kg) vs placebo of 2.7 (95% CI: 2.0-3.6; p < 0.001). However, in the validate dataset the odds ratio was not significant at 1.3 (95% CI: 0.8-2.2; p = 0.863). Conclusions The index created from training data did not achieve statistical significance when tested in the validation set. We have speculated why this happened. Is the lack of success of therapeutics for SLE caused by ineffective medications, study design and outcome instruments that fail to inform us, or is the heterogeneity of the disease too daunting? The lessons learned here can help direct future endeavors intended to improve SLE outcome instruments.

Anti-C1q antibodies in systemic lupus erythematosus.

OBJECTIVE: Anti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs rheumatic disease controls) and the association with SLE manifestations in an international multicenter study. METHODS: Information and blood samples were obtained in a cross-sectional study from patients with SLE (n = 308) and other rheumatologic diseases (n = 389) from 25 clinical sites (84% female, 68% Caucasian, 17% African descent, 8% Asian, 7% other). IgG anti-C1q against the collagen-like region was measured by ELISA. RESULTS: Prevalence of anti-C1q was 28% (86/308) in patients with SLE and 13% (49/389) in controls (OR = 2.7, 95% CI: 1.8-4, p < 0.001). Anti-C1q was associated with proteinuria (OR = 3.0, 95% CI: 1.7-5.1, p < 0.001), red cell casts (OR = 2.6, 95% CI: 1.2-5.4, p = 0.015), anti-dsDNA (OR = 3.4, 95% CI: 1.9-6.1, p < 0.001) and anti-Smith (OR = 2.8, 95% CI: 1.5-5.0, p = 0.01). Anti-C1q was independently associated with renal involvement after adjustment for demographics, ANA, anti-dsDNA and low complement (OR = 2.3, 95% CI: 1.3-4.2, p < 0.01). Simultaneously positive anti-C1q, anti-dsDNA and low complement was strongly associated with renal involvement (OR = 14.9, 95% CI: 5.8-38.4, p < 0.01). CONCLUSIONS: Anti-C1q was more common in patients with SLE and those of Asian race/ethnicity. We confirmed a significant association of anti-C1q with renal involvement, independent of demographics and other serologies. Anti-C1q in combination with anti-dsDNA and low complement was the strongest serological association with renal involvement. These data support the usefulness of anti-C1q in SLE, especially in lupus nephritis.

Association study of genes related to bone formation and resorption and the extent of radiographic change in ankylosing spondylitis.

OBJECTIVE: To identify genetic associations with severity of radiographic damage in ankylosing spondylitis (AS). METHOD: We studied 1537 AS cases of European descent; all fulfilled the modified New York Criteria. Radiographic severity was assessed from digitised lateral radiographs of the cervical and lumbar spine using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). A two-phase genotyping design was used. In phase 1, 498 single nucleotide polymorphisms (SNPs) were genotyped in 688 cases; these were selected to capture >90% of the common haplotypic variation in the exons, exon-intron boundaries, and 5 kb flanking DNA in the 5' and 3' UTR of 74 genes involved in anabolic or catabolic bone pathways. In phase 2, 15 SNPs exhibiting p<0.05 were genotyped in a further cohort of 830 AS cases; results were analysed both separately and in combination with the discovery phase data. Association was tested by contingency tables after separating the samples into 'mild' and 'severe' groups, defined as the bottom and top 40% by mSASSS, adjusted for gender and disease duration. RESULTS: Experiment-wise association was observed with the SNP rs8092336 (combined OR 0.32, p=1.2×10(-5)), which lies within RANK (receptor activator of NFκB), a gene involved in osteoclastogenesis, and in the interaction between T cells and dendritic cells. Association was also found with the SNP rs1236913 in PTGS1 (prostaglandin-endoperoxide synthase 1, cyclooxygenase 1), giving an OR of 0.53 (p=2.6×10(-3)). There was no observed association between radiographic severity and HLA-B*27. CONCLUSIONS: These findings support roles for bone resorption and prostaglandins pathways in the osteoproliferative changes in AS.

Smoking is not associated with autoantibody production in systemic lupus erythematosus patients, unaffected first-degree relatives, nor healthy controls.

OBJECTIVE: The objective of this paper is to examine whether smoking is associated with autoantibody production in systemic lupus erythematosus (SLE) patients, unaffected first-degree relatives (FDR) of individuals with SLE--a group at increased risk of developing SLE--or unaffected, unrelated controls. METHODS: Detailed demographic, environmental, clinical, and therapeutic information was collected by questionnaire on 1242 SLE patients, 981 FDRs, and 946 controls in the Lupus Family Registry and Repository; a blood sample was obtained. All sera were tested for multiple lupus autoantibodies by immunofluorescence and luminex bead-based assays. Generalized estimating equations, adjusting for age, gender, and ethnicity and accounting for correlation within families, were used to assess smoking status with the dichotomous outcome variables of positivity for SLE status, positivity of ANA by immunofluorescence (≥1:120), positivity for ≥1 autoantibody by the luminex assay, and positivity for each of the 11 autoantibodies. RESULTS: Current smoking was associated with being positive for ≥1 autoantibody (excluding ANA) (adjusted OR = 1.53, 95% CI 1.04-2.24) in our subjects with SLE. No association was observed in unaffected FDRs or healthy controls. Former smoking was associated with anti-Ro/SS-A60 in our unaffected FDRs. There was an increased association with anti-nRNP A seropositivity, as well as a decreased association with anti-nRNP 68 positivity, in current smokers in SLE subjects. CONCLUSIONS: No clear association between smoking status and individual autoantibodies was detected in SLE patients, unaffected FDRs, nor healthy controls within this collection. The association of smoking with SLE may therefore manifest its risk through mechanisms outside of autoantibody production, at least for the specificities tested.

The Patient Reported Outcomes in Lupus (PATROL) study: role of depression in health-related quality of life in a Southern California lupus cohort.

UNLABELLED: This study examines the relationship between psychosocial factors, ethnicity, disease activity and quality of life in systemic lupus erythematosus. METHODS: One hundred and twenty-five adult Caucasian and Hispanic lupus patients were recruited from four Southern California medical centers. Linear regression analysis was performed to assess the correlation of ethnicity, socioeconomic factors (age, income), and disease activity (patient and physician reported), as well as psychological (depression, internality, helplessness) variables with quality of life (QOL) as measured by the Short Form (SF)-36. Hierarchical multiple regression analysis was then used to determine the stepwise contribution of the above determinants on the eight domains of the SF-36 questionnaire. RESULTS: Depression negatively correlated with QOL in both Caucasians (r -0.488 to -0.660) and Hispanics (r -0.456 to -0.723). Patient-reported disease activity was moderately related (r -0.456 to -0.698) to seven of the eight SF-36 domains in Hispanics, and none in Caucasians. Physician-reported disease activity, measured by SLEDAI, did not correlate with QOL among Hispanics or Caucasians. When linear and hierarchical regression was used, depression significantly correlated (p < 0.0001) with the majority of the SF-36 domains, except general health, while age had a significant effect in only one domain of the SF-36, physical functioning (p < 0.0001). CONCLUSION: Depression, and not disease activity, appears to have a major influence on quality of life in both Hispanic and Caucasian patients in this lupus cohort.

High-sensitivity C-reactive protein and erythrocyte sedimentation rate in systemic lupus erythematosus.

Levels of C-reactive protein (CRP) have been shown to rise in acute illnesses such as infections and some autoimmune diseases, but not in flares of systemic lupus erythematosus (SLE). Our goal was to investigate the high-sensitivity CRP (hsCRP) response to infection versus disease flare in patients with SLE, and to compare this with the erythrocyte sedimentation rate (ESR) response in these patients. We aimed to determine the hsCRP level that distinguishes between infection and flare in SLE, and investigated the correlation between hsCRP and organ involvement in SLE. We reviewed electronic medical records of all patients with SLE admitted to Cedars Sinai Medical Center between 28 August 2001 and 27 April 2008. Patients were divided into three groups based on the reason for hospitalization: (1) lupus flare; (2) active infection; and (3) both lupus flare and active infection. Data were collected on patient demographics, medication use, microbial culture results, organ involvement in lupus flare, ESR and CRP levels. Data were collected on 85 eligible patients, of whom 54 had a lupus flare, 22 had active infection and eight had both. While the ESR levels did not differ significantly between patients with disease flare and active infection, the hsCRP level was significantly lower in the lupus flare group than in the infection group. Most patients in the lupus flare group who had a significantly high hsCRP level had serositis. We found that at a cut-off of above 5 mg/dl, hsCRP level was correlated with infection with a specificity of 80%. At a cut-off of above 6 mg/dl, hsCRP correlated with infection with a specificity of 84%. hsCRP level was found to be significantly higher in patients with pulmonary involvement than without. hsCRP levels are significantly lower in SLE patients with disease flare than in those with active infection. Elevated hsCRP levels can be used as a predictor of active infection in SLE patients with a high specificity. We review the relationship between IL-6 and hsCRP production in lupus patients.

Depression predicts self-reported disease activity in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease that can significantly impact both physiological and psychological functioning. In order to examine the relationship between psychological functioning and disease activity in SLE, we administered instruments that collected sociodemographic information and measured indices of disease activity and psychosocial functioning from 125 adult Hispanic and White patients with SLE. Patients were recruited from four healthcare settings in the greater Southern California area. Both cross-sectional and longitudinal relationships between depression and disease activity were evaluated. Cross-sectional findings revealed that depression and ethnicity were independently correlated with self-reported disease activity. Longitudinally, depression alone predicted self-reported disease activity. These data suggest that depression may play a significant role in the health status of SLE patients and serve as an important target for clinical intervention.

Studies of Filipino patients with systemic lupus erythematosus: autoantibody profile of first-degree relatives.

This study surveyed the frequency of autoantibodies among un-affected first-degree relatives (FDRs) of Filipino systemic lupus erythematosus (SLE) patients compared with healthy un-related Filipino controls. The sensitivity, specificity and predictive value of the autoantibodies for SLE diagnosis were also assessed in this Filipino cohort. Filipino patients included in the University of Santo Tomas (UST) Lupus Database and un-affected FDRs were recruited. Healthy controls included those with no known personal or family history of autoimmune disease. The following autoantibodies were tested in all subjects: anti-nuclear antibody (ANA), anti-dsDNA, anti-Ro/SSA, anti-chromatin, anti-thyroid microsome, and anti-cardiolipin antibodies. Participants included 232 SLE patients, 546 FDRs, and 221 healthy controls. Median age of patients was 27 (range 8-66) years with median disease duration of 27.5 (range 1-292) months. Median age of FDRs was 42.0 (range 5-87) years. Compared with healthy controls, there were significantly more FDRs with positive ANA at titers 1 : 40 to 1 : 160 (p < 0.001) and 1 : 320 (p = 0.003), anti-Ro/SSA (4.94% versus 0.45%, p = 0.003), and anti-dsDNA ≥ 5.0 IU/ml (4.58% versus 1.36%, p = 0.031). ANA titer ≥1 : 160, anti-dsDNA, anti-Ro/SSA and anti-chromatin had the highest predictive value for SLE diagnosis. These findings reinforce the role of genetic influence in SLE risk among Filipinos, with a significant proportion of un-affected FDRs of SLE patients testing positive for autoantibodies compared with healthy Filipino controls. A longitudinal observational study in this same cohort will determine which proportion of these un-affected FDRs will evolve into clinical SLE disease in the future.

Review: Male systemic lupus erythematosus: a review of sex disparities in this disease.

Although males with systemic lupus erythematosus (SLE) represent 4-22% of all SLE patients, it may not be appropriate that these cases should be subordinated to females with SLE in terms of most health-related issues. Over the past few decades, some distinctive features of male lupus have been observed with regard to genetic and environmental aspects of sex differences, clinical features, and outcome. In addition, recent insights into sex disparities in this disease have brought forth a few plausible and novel pathogenetic hypotheses. This review discusses these findings and sex disparities in SLE that appear to be especially noteworthy and pertinent to our understanding of male SLE.

Does mycophenolate mofetil prevent extra-renal flares in systemic lupus erythematosus? Results from an observational study of patients in a single practice treated for up to 5 years.

In this study, the clinical course and change in extra-renal manifestations of patients with SLE taking mycophenolate mofetil (MMF) were evaluated. The charts of 75 consecutively identified patients on MMF from a single practice were reviewed for demographics, dates of SLE diagnosis, initiation, indication or discontinuation of MMF and other medications. British Isles Lupus Assessment Group (BILAG) organ system data were identified for 3 months prior to MMF and then for the subsequent 5 years. BILAG scores for each organ system and an overall score were calculated for intervals of 6 months. The mean age of 75 subjects was 35.8 years with SLE mean disease duration of 99.2 months. Indications for starting MMF were renal (70.7%), musculoskeletal (10.6%), mucocutaneous (9.3%), cardiorespiratory (5.3%), haematologic (4%), vasculitic (2.7%), neurologic (1.3%) and other (18.7%). The mean duration of treatment was 3.3 years; 22 discontinuations occurred. Overall, there was a >50% improvement in composite BILAG scores for 49.3% (37/75) of patients in the first year of treatment and in 20% (15/75) of patients who were still on MMF at >or=5 years. Most flares occurred at second and third year of treatment. The general and renal systems have the most improvement and clinical remissions; the musculoskeletal, mucocutaneous and haematological systems have the most recurrences. Approximately, 50% and 20% of patients taking MMF showed improvement in overall lupus disease activity at both 1 and 5 years, respectively. When evaluating organ system subsets separately, MMF improved disease activity in the first year, but had little effect in preventing new organ-specific flares, with most flares taking place in second and third year of treatment.