Does higher quality of care in systemic lupus erythematosus translate to better patient outcomes?

PURPOSE: To assess if high quality of care (QOC) in SLE results in improved outcomes of quality of life (QOL) and non-routine health care utilization (HCU). METHODS: One hundred and forty consecutive SLE patients were recruited from the Rheumatology clinic at an academic center. Data on QOC and QOL were collected along with demographics, socio-economic, and disease characteristics at baseline. LupusPRO assessing health-related (HR) QOL and non (N)HRQOL was utilized. Follow up QOL and HCU were collected prospectively at 6 months. High QOC was defined as those meeting ≥80% of the eligible quality indicators. Univariate and multivariate regression analyses were performed with QOC and high QOC as independent variables and HRQOL and NHRQOL as dependent variables at baseline and follow up. Multivariable models were adjusted for demographics and disease characteristics. Secondary outcomes included non-routine HCU and disease activity at follow up. RESULTS: Baseline and follow up data on 140 and 94 patients, respectively, were analyzed. Mean (SD) performance rate (QOC) was 78.6 (13.4) with 52% patients in the high QOC group. QOC was associated with better NHRQOL at baseline and follow up but not with HRQOL. Of all the NHRQOL domains, QOC was positively associated with treatment satisfaction. QOC or high QOC were not associated with non-routine HCU and were instead associated with higher disease activity at follow up. CONCLUSION: Higher QOC predicted better NHRQOL by directly impacting treatment satisfaction in SLE patients in this cohort. Higher QOC, however, was not associated with HRQOL, HCU, or improvement in disease activity at follow up.

Korean LupusPRO: Cross-Cultural validation study for systemic lupus erythematosus.

OBJECTIVE: To establish the reliability and validity of the Korean version of LupusPRO version 1.7 (v1.7) for systemic lupus erythematosus (SLE) patients. METHODS: LupusPRO v1.7 was translated into Korean, followed by pretesting among five native Korean speakers. We administered the LupusPRO v1.7 survey to five SLE patients and made minor changes to clarify the language. Then, 133 SLE patients participated in the validation procedure. In each domain, the internal consistency reliability (ICR) and test-retest reliability (TRR) were assessed using Cronbach's alpha and the intra-class correlation coefficient (ICC), respectively. Criterion validity was evaluated using Spearman's correlation coefficient with the other measures such as SF-36, EQ-5D VAS, and SELENA-SLEDAI PGA. Construct validity was assessed by confirmatory factor analysis (CFA) using the unweighted least square estimation method. RESULTS: The mean age of the 133 patients was 36.14 years, and 97% of them were women. Analysis of 130 returned questionnaires revealed that most ICRs of the Korean LupusPRO v1.7 domains were acceptable, with Cronbach's alphas in the range of 0.579-0.949, and most TRRs were good with ICCs from 0.582 to 0.851. Criterion validities presented significant correlations between the LupusPRO v1.7 and other measures validated. In the analysis of the CFA model, the goodness of fit indices demonstrated an acceptable fit. Factor loadings for most individual items were between 0.548 and 0.985. The average variance extracted (AVE) and composite reliability (CR) of most domains were greater than 0.5 and 0.7, respectively, demonstrating acceptable convergent and discriminant validities. CONCLUSIONS: The Korean version of LupusPRO v.17 had acceptable reliability and validity.

Does hydroxychloroquine improve patient reported outcomes in patients with lupus?

BACKGROUND: Hydroxychloroquine (HCQ) use is associated with less disease activity, flares, damage and improved survival in Systemic Lupus Erythematosus (SLE). However, its effect on patient reported health outcomes (PROs) such as quality of life (QOL) is not known. METHODS: International data from Study on Outcomes of Lupus (SOUL) from 2,161 SLE patients were compared by HCQ use. Disease activity and damage were assessed using SELENA-SLEDAI and SLICC-ACR/SDI. QOL was evaluated using LupusPRO and Lupus Impact Tracker (LIT). Linear regression analyses were performed with LupusPRO summary scores health related HRQOL, non-health related NHRQOL and LIT as dependent and HCQ use as independent variable. Analyses were undertaken to test mediation of effects of HCQ use on QOL through disease activity. RESULTS: Mean age was 40.5 ± 12.8 years, 93% were women. Sixty-three (1363/2161) percent were on HCQ. On univariate analysis, HCQ use was associated with (a) better QOL (LupusPRO-HRQOL: ß 6.19, 95% CI 4.15, 8.24, P ≤ 0.001, LupusPRO NHRQOL: ß 5.83, 95% CI 4.02, 7.64, P ≤ 0.001) and less impact on daily life (LIT: ß -9.37, 95% CI -12.24, -6.50, P ≤ 0.001). On multivariate and mediational analyses, the effects of HCQ on QOL were indirectly and completely mediated through disease activity. CONCLUSIONS: HCQ use in SLE is associated with better patient reported health outcomes (LupusPRO-HRQOL and NHRQOL and impact on daily life), and the effects are mediated through disease activity. This information can facilitate patients and physician's communication with decision-making regarding the use of HCQ for SLE management.

Pneumococcal Vaccination Among Lupus Patients: Who Are the Recipients?

PURPOSE: Pneumococcal vaccination (PV) is indicated for the elderly (age ≥65 years) and those with chronic disease or who are immunosuppressed. We aimed to study the rate and predictors of recommendation/receipt of 23 valent pneumococcal polysaccharide vaccine (PPSV23) in immunosuppressed systemic lupus erythematosus (SLE) patients. METHODS: Data were obtained through self-report questionnaires and medical chart review of 150 SLE patients. Information on rheumatologist recommendation or receipt of PPSV23 in the preceding 5 years was collected if self-reported in a questionnaire or documented in the medical chart. Chart review was also done to collect data on patient demographics, physician characteristics (if patients had a primary care physician and rheumatologist's SLE patient volume), and the disease characteristics of SLE. Comparisons using χ2 or t tests and logistic regression analyses were conducted for predictors of recommendation/receipt of PV. RESULTS: The mean (SD) age was 47.4 (15.9) years; 90% were women. Sixty-five of 94 eligible patients for PV (based on immunosuppressive medications use or age) had been either recommended or administered PPSV23. On univariate logistic regression analysis, age, duration of disease, current use of hydroxychloroquine or mycophenolate, and rheumatologist's SLE patient volume were significant correlates of recommendation/receipt of PPSV23. However, on multivariate analysis, the only significant predictor was rheumatologist's SLE patient volume after adjusting for the above correlates such that with every 50 patients increase in SLE patient clinic volume, the odds of recommendation/receipt of PPSV23 increased by 2.37 times. CONCLUSIONS: The volume of lupus patients that rheumatologists see is strongly associated with the likelihood that their SLE patients will have PPSV23 recommended and delivered, suggesting a volume outcome relationship.

Performance and psychometric properties of lupus impact tracker in assessing patient-reported outcomes in pediatric lupus: Report from a pilot study.

OBJECTIVE: To evaluate the reliability, validity, feasibility and psychometric performance of the Lupus Impact Tracker (LIT) as a patient reported outcome (PRO) measure tool in pediatric systemic lupus erythematosus (pSLE). METHODS: This is a prospective, observational, pilot study where patients aged between 12 and 25 years, fulfilling the 1997 ACR classification criteria for SLE, were enrolled. Over 3 consecutive, routine, clinical visits, the patients completed the LIT alongside the Patient-Reported Outcomes Measurement Information System-Short Forms (PROMIS-SFs), Childhood Health Assessment Questionnaire (CHAQ). Rheumatologists completed the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC-ACR) Damage Index. Demographic, clinical and laboratory data were also collected. RESULTS: Of 46 patients enrolled, 38 patients completed 2 visits and 31 completed all 3 visits. Seventy-eight percent were female, 33% African American, 28% Asian, 15% Caucasian and 17% Hispanic. The mean (SD) age was 17.2 (2.7) years, with a mean (SD) disease duration of 4.6 (3.1) years. The mean (SD) SLEDAI-2K at enrollment was 3.54 (2.96). In the 38 patients who completed two or more visits, intra-class correlation coefficient and Cronbach alpha were calculated to be 0.70 and 0.91 respectively, signifying good reliability of LIT. The LIT showed positive correlation with CHAQ-Disability Index and majority of the PROMIS-SFs parameters. Construct validity was established against clinical disease activity (SLEDAI-2K). CONCLUSION: The preliminary results indicate that the LIT is a reliable and valid instrument to capture PRO in p-SLE. Prospective validation with a larger, multicenter cohort is the next step.

The Arabic LupusPRO: A Cross-Cultural Validation of a Disease-Specific Patient-Reported Outcome Tool for Quality of Life in Lupus Patients.

OBJECTIVE: To translate and cross-culturally adapt the Arabic version of LupusPRO v.1.8 and to test its reliability and validity. METHODS: LupusPRO was translated into the Arabic language following a standard procedure with forward-backward translation and was tested in patients with systemic lupus erythematosus (SLE) before use. The Arabic version was administered to 107 Egyptian SLE patients, along with a validated Arabic version of RAND 36-Item Health Survey 1.0 (SF-36). The internal consistency and test-retest reliability were determined. Validity was assessed by correlating LupusPRO scores with SF-36, Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). The conceptual framework of the Arabic LupusPRO was evaluated using confirmatory factor analysis (CFA). RESULTS: Among the 107 SLE patients, 95% were women with a median (range) age of 32 (18-55) years, median (range) SELENA-SLEDAI of 6 (0-23) and median (range) SDI of 0 (0-6). The Cronbach's alpha for the Arabic LupusPRO ranged from 0.71 to 0.98, except for the social support domain (0.65). Test-retest reliability ranged from 0.95 to 0.99. Convergent validity with corresponding domains of SF 36 was satisfactory. For criterion validity, there was a weak but significant correlation between several LupusPRO domains with SELENA-SLEDAI. CFA showed a good model fit. CONCLUSION: The Arabic version of LupusPRO v1.8 is a reliable and valid tool for measuring quality of life among Arabic speaking SLE patients.

Serologic features of cohorts with variable genetic risk for systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease with genetic, hormonal, and environmental influences. In Western Europe and North America, individuals of West African descent have a 3-4 fold greater incidence of SLE than Caucasians. Paradoxically, West Africans in sub-Saharan Africa appear to have a low incidence of SLE, and some studies suggest a milder disease with less nephritis. In this study, we analyzed sera from African American female SLE patients and four other cohorts, one with SLE and others with varying degrees of risk for SLE in order to identify serologic factors that might correlate with risk of or protection against SLE. METHODS: Our cohorts included West African women with previous malaria infection assumed to be protected from development of SLE, clinically unaffected sisters of SLE patients with high risk of developing SLE, healthy African American women with intermediate risk, healthy Caucasian women with low risk of developing SLE, and women with a diagnosis of SLE. We developed a lupus risk index (LRI) based on titers of IgM and IgG anti-double stranded DNA antibodies and levels of C1q. RESULTS: The risk index was highest in SLE patients; second highest in unaffected sisters of SLE patients; third highest in healthy African-American women and lowest in healthy Caucasian women and malaria-exposed West African women. CONCLUSION: This risk index may be useful in early interventions to prevent SLE. In addition, it suggests new therapeutic approaches for the treatment of SLE.

Validation of SIMPLE Index for Lupus Disease Activity.

OBJECTIVE: An easy, quick tool requiring minimal training or health care provider input would potentially have greater uptake for clinical use among rheumatologists and primary care physicians for assessment of disease activity in systemic lupus erythematosus (SLE). SIMPLE (SIMple Disease Assessment for People with Lupus Erythematosus) index is a composite numeric tool that is easy and quick to calculate. We prospectively assessed the performance of the SIMPLE index as a disease activity surrogate against physician-based disease activity measures. METHODS: Ninety-nine consenting patients meeting American College of Rheumatology SLE classification criteria were recruited. Safety of Estrogen in Lupus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI), physician global assessment, and SIMPLE index were obtained during routine visits. SIMPLE index is a 17-item patient-reported questionnaire that includes 2 laboratory tests. Health care provider input is needed only to provide laboratory results (normal/abnormal) and confirming patient-reported current use and dosing of glucocorticoids. We performed Spearman test to assess correlation of SIMPLE index with SELENA-SLEDAI and physician global assessment. RESULTS: Mean age (SD) was 39.7 (12.3) years. The correlation coefficient between SIMPLE index and SELENA-SLEDAI was 0.56 (P = 0.0001), and that between SIMPLE index and physician global assessment was 0.54 (P = 0.0001). In SLE patients without fibromyalgia (FM), the correlation of SIMPLE index with SELENA-SLEDAI and physician global assessment was 0.58 (P = 0.0001) and 0.57 (P = 0.0001), respectively. CONCLUSIONS: SIMPLE index is strongly correlated with formal physician assessments of disease activity in SLE, and correlation was marginally higher among those without FM. SIMPLE index can be performed easily in places with limited physician and laboratory resources.

Body image intervention to improve health outcomes in lupus: a pilot study.

PURPOSE: Systemic lupus erythematosus (SLE) can be disfiguring, disabling, and debilitating. In this proof-of-concept study, our goal was to determine the feasibility and effectiveness of a novel body image (BI) intervention in improving (1) BI and (2) health outcomes among women with cutaneous SLE. METHODS: A tailored weekly intervention for 10 weeks consisting of education, cognitive behavioral therapy, and cosmetic training was offered, along with usual fscare, to 10 SLE patients with inactive to mildly active disease and cutaneous involvement. For comparison, we followed up 5 patients with inactive to mildly active SLE and cutaneous involvement, receiving only usual care. Data on outcomes were obtained at baseline, immediately postintervention, and 18 and 24 weeks postintervention using the following tools: Body Image in Lupus Scale (BI), Multidimensional Body Self-Relations Questionnaire-Appearance Scale, State Trait Anxiety Index and Center for Epidemiological Studies Depression (psychological health), and LupusPRO (lupus health outcomes). Paired t tests (2-tailed) were done for between-groups comparisons. P ≤ 0.05 was considered significant. RESULTS: The mean ages of the intervention and control groups were 44.4 (SD, 8.7) and 43.2 (SD, 12.2) years, respectively. Scores on measures of BI, psychological well-being, and quality of life improved over time only in the intervention group; the benefits were retained over time. The observed effect size of the improvements in BI was large. CONCLUSIONS: Body image is modifiable in SLE. The results suggest that our intervention is feasible for SLE populations and that the SLE patients who participated improved on several measures of BI and overall well-being.

Use and Utility of Patient After-Visit Instructions at a University Rheumatology Outpatient Clinic: Status and Randomized Prospective Pilot Intervention Study.

OBJECTIVE: The aim of this study was to evaluate the use of after-visit instructions (AVIs) in an academic rheumatology clinic and assess the impact of standardized AVIs (sAVIs) and teach-back (TB) on comprehension of health information. METHODS: A retrospective review of adult patients seen between October 1 and 8, 2021, at the rheumatology clinic collected data on patient demographics, clinical features, and the presence, content, and readability of AVIs. During a subsequent prospective proof-of-concept study, routinely scheduled patients seen at the rheumatology clinic were randomized into three groups: control (received standard of care), received sAVIs only, and received sAVIs plus TB. Patients completed a health literacy questionnaire, satisfaction survey, and a one- to two-week postvisit telephone survey to assess AVI comprehension. RESULTS: Out of 316 retrospective patient visits, 82 (25.9%) received AVIs. Among 210 of 316 patients (66.5%) with management changes, 76 (36.1%) received AVI, with 74.2% of the instructions considered concordant with the provider's note. Use of AVIs was higher with management changes, new patient visits, and medical trainee/teaching clinics. AVIs were written at a median 6.8 grade level. A total of 75 patients completed the prospective study: 31 (41.3%) were in the control group, 19 (25.3%) were in the group that received sAVIs only, and 25 (33.3%) were in the group that received AVIs with TB. There were no differences in overall postvisit survey comprehension/retention scores among the three patient groups evaluated. CONCLUSION: Although a lack of AVI use was identified, implementation of sAVIs did not appear to impact patient retention or comprehension of discharge health information.

Top 10 recent developments in health-related quality of life in patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that has major implications for health-related quality of life (HRQoL). Improvements in the monitoring and management of SLE improves survival; however, improvement of HRQoL remains of paramount importance among these patients. Measurement of HRQoL has been recommended in clinical practice and research including drug development and testing in clinical trials. Both generic and disease specific instruments have been developed to ascertain HRQoL. In an increasingly global collaborative environment, the importance of assessing HRQoL across nations, acknowledgment of their confounders, and limitations of used instruments are critical. Here, we review selected major developments in the past 5 years highlighting: the importance of measuring HRQoL in SLE patients, the benefits and limitations of instruments that exist, and their application in research settings.

Validation of the Cutaneous Lupus Disease Area and Severity Index (CLASI) using physician- and patient-assessed health outcome measures.

BACKGROUND: The Cutaneous Lupus Disease Area and Severity Index (CLASI) has not been validated using rheumatologist-conducted disease activity and damage assessments, especially cutaneous assessments. Active skin disease and skin damage may have substantial effects on patient-reported outcomes and on body image. OBJECTIVE: We sought to validate the CLASI against: (1) physician-assessed disease activity and damage measures; and (2) patient-reported assessment of quality of life and body image. METHODS: Cross-sectional data were collected from 31 patients with cutaneous lupus erythematosus. Cutaneous disease activity and damage were measured by using the CLASI. Disease activity (using the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus [SLE] Disease Activity Index [SLEDAI}), damage (Systemic Lupus International Collaboration Clinics-American College of Rheumatology Damage Index [SDI]), quality of life (LupusPRO), and body image (Body Image Quality of Life Inventory) were obtained. Descriptive statistics and Spearman correlations were ascertained. RESULTS: Mean (SD) age was 42.3 (12.8) years; 97% were women. The mean (SD) CLASI activity and damage scores were 10.5 (7.4) and 9.9 (9.5). Correlations noted were: total CLASI activity and SLEDAI-rash (r = 0.42, P = .02), CLASI-mucosal and SLEDAI-mucosal (r = 0.65, P = .001), CLASI-recent hair loss and SLEDAI-alopecia (r = 0.61, P = .001), and total CLASI activity and LupusPRO symptoms domain (r = -0.38, P = .04). Total CLASI-damage correlated with SDI-scarring/alopecia (r = 0.51, P = .004), SDI-extensive scarring/panniculum (r = 0.55, P = .003), and SDI-skin ulceration (r = 0.36, P = .05). CLASI scalp scarring correlated with SDI-skin scarring/alopecia (r = 0.94, P = .001). CLASI activity on the face and nose was associated with significant concerns on the Body Image Quality of Life Inventory. LIMITATIONS: Limitations include small sample size. CONCLUSION: CLASI activity and damage scores correlate with physician-assessed cutaneous activity and damage in cutaneous lupus erythematosus in patients with SLE. Cutaneous activity in visible areas may generate body image concerns.

Autoimmune disease risk variant of IFIH1 is associated with increased sensitivity to IFN-α and serologic autoimmunity in lupus patients.

Increased IFN-α signaling is a heritable risk factor for systemic lupus erythematosus (SLE). IFN induced with helicase C domain 1 (IFIH1) is a cytoplasmic dsRNA sensor that activates IFN-α pathway signaling. We studied the impact of the autoimmune-disease-associated IFIH1 rs1990760 (A946T) single nucleotide polymorphism upon IFN-α signaling in SLE patients in vivo. We studied 563 SLE patients (278 African-American, 179 European-American, and 106 Hispanic-American). Logistic regression models were used to detect genetic associations with autoantibody traits, and multiple linear regression was used to analyze IFN-α-induced gene expression in PBMCs in the context of serum IFN-α in the same blood sample. We found that the rs1990760 T allele was associated with anti-dsDNA Abs across all of the studied ancestral backgrounds (meta-analysis odds ratio = 1.34, p = 0.026). This allele also was associated with lower serum IFN-α levels in subjects who had anti-dsDNA Abs (p = 0.0026). When we studied simultaneous serum and PBMC samples from SLE patients, we found that the IFIH1 rs1990760 T allele was associated with increased IFN-induced gene expression in PBMCs in response to a given amount of serum IFN-α in anti-dsDNA-positive patients. This effect was independent of the STAT4 genotype, which modulates sensitivity to IFN-α in a similar way. Thus, the IFIH1 rs1990760 T allele was associated with dsDNA Abs, and in patients with anti-dsDNA Abs this risk allele increased sensitivity to IFN-α signaling. These studies suggest a role for the IFIH1 risk allele in SLE in vivo.

Posterior reversible encephalopathy syndrome in systemic lupus erythematosus.

BACKGROUND/OBJECTIVE: Posterior reversible encephalopathy syndrome (PRES) is an underrecognized and reversible condition in systemic lupus erythematosus (SLE) that could mimic neuropsychiatric lupus. Identification of any distinct clinical patterns is important as one would need to escalate rather than decrease or discontinue immune suppression in neuropsychiatric lupus. METHODS: We retrospectively identified and described 5 patients with SLE who were hospitalized and diagnosed with PRES from 2008 to 2013 in a tertiary medical center and reviewed relevant literature. RESULTS: Posterior reversible encephalopathy syndrome in SLE occurred in young women with age distribution from 19 to 37 years. At the time of presentation, all had hypertension (systolic blood pressures ranging from 150 to 220), moderate to severe disease activity (Systemic Lupus Erythematosus Disease Activity Index scores ranging from 11 to 41), and prototypical magnetic resonance imaging findings of PRES and nephritis (4 of 5 patients had biopsy-proven lupus nephritis). Seizures, headache, and confusion were the most common clinical symptoms. One patient had intracerebral hematoma, and 2 patients had cerebral petechial hemorrhages. All patients improved without any neurological deficits, with a mean hospital stay of 11.2 days. CONCLUSIONS: Systemic lupus erythematosus should be considered in the differential diagnosis of patients who present with PRES. One should have a low threshold for magnetic resonance imaging especially when neurological symptoms occur in young women with or without an established diagnosis of SLE and especially among those with active SLE, lupus nephritis, renal failure, and/or poorly controlled hypertension. Given the good prognosis of PRES in SLE patients with early supportive treatment, prompt recognition is crucial to institute appropriate management.

Assessing readability and comprehension of web-based patient education materials by American Heart Association (AHA) and CardioSmart online platform by American College of Cardiology (ACC): How useful are these websites for patient understanding?

Cardiovascular diseases (CVD) are a leading cause of morbidity & mortality worldwide. Patient education materials help patients understand the disease and its management. Health literacy is an important challenge that may contribute to health inequities and disparities. The National Institute of Health and American Medical Association recommend patient education materials to be ≤6th-grade reading level. Objective: To evaluate readability and comprehension of patient education materials related to CVD, available at the American Heart Association (AHA) & CardioSmart web platform by the American College of Cardiology (ACC) websites. Method: We examined the readability and comprehension of 63 patient education materials (accessed June 2022) using: (a) Flesch Kincaid Readability Ease (FKRE): measures readability (0-100, goal > 70), (b) Flesch Kincaid Grade Level (FKGL) (goal = grade 7). We compared the AHA and ACC scores using descriptive and t-tests. P-value ≤ 0.05 was significant. Results: Sixty-three web pages of patient education materials (AHA 24, ACC 39) were reviewed in June 2022. Mean ± standard deviation (SD) FKRE was 54.9 ± 6.8 for all the web pages. FKRE 50-60 equates to "fairly difficult to read." Mean ± SD FKGL was 10.0 ± 1.3. AHA patient education materials content was significantly more difficult to read and comprehend, were longer, and had more complex words than ACC patient education materials. Conclusions: CVD-related patient education materials available online through leading national organizations are not congruent with the recommendations from national healthcare organizations. They are not as user-friendly as they can be. Urgent recognition of the gaps and unmet needs are indicated to optimize patient health literacy.

Does Higher Quality of Care in Systemic Lupus Erythematosus Improve Quality of Life?

OBJECTIVE: To study the association between high quality of care (QOC) and quality of life (QOL) and nonroutine health care use (HCU) in systemic lupus erythematosus. METHODS: Data were derived from 814 participants from the Lupus Outcomes Study sample. Data on sociodemographic information, disease status, medications, and health care variables were collected through annual interviews. QOC was measured at baseline on 13 quality indices amenable to self-report. Follow-up QOL was measured using the Short Form 36 health survey (SF-36) 2 years later. Univariate and multivariate regression analyses assessed the relationship between QOC and SF-36 scores at baseline, and logistic regression analyses evaluated QOC at baseline as a predictor of minimal clinically important difference (MCID) improvements in SF-36 scores, emergency room (ER) visits, and hospitalizations at follow-up. RESULTS: Higher QOC was associated with worse scores on SF-36 domains on univariate analysis at baseline, which was mediated by comorbidities and high disease activity. QOC and the number of years in high QOC were not predictive of MCID improvements in SF-36 scores at follow-up, which were driven by baseline SF-36 scores, disease activity, and nonroutine HCU. A similar pattern was noted for ER visits and hospitalizations, for which disease activity, damage, and glucocorticoid dose were significant predictors and not QOC. CONCLUSION: High QOC at baseline and the number of years with high QOC are not associated with MCID improvement in SF-36 scores and nonroutine HCU on follow-up. High QOC, as determined by currently defined criteria, serves as a surrogate of greater disease activity, morbidity, and nonroutine HCU.

Network analysis of associations between serum interferon-α activity, autoantibodies, and clinical features in systemic lupus erythematosus.

OBJECTIVE: Interferon-α (IFNα) is a primary pathogenic factor in systemic lupus erythematosus (SLE), and high IFNα levels may be associated with particular clinical manifestations. The prevalence of individual clinical and serologic features differs significantly by ancestry. This study was undertaken to detect associations between clinical and serologic disease manifestations and serum IFNα activity in a large diverse SLE cohort, using multivariate and network analyses. METHODS: We studied 1,089 SLE patients (387 African American, 186 Hispanic American, and 516 European American patients). The presence or absence of individual American College of Rheumatology (ACR) clinical criteria for SLE, autoantibodies, and serum IFNα activity data were analyzed in univariate and multivariate models. Iterative multivariate logistic regression was performed in each ancestral background group separately to establish the network of associations between variables that were independently significant following Bonferroni correction. RESULTS: In all ancestral backgrounds, high IFNα activity was associated with anti-Ro and anti-double-stranded DNA antibodies (P = 4.6 × 10(-18) and P = 2.9 × 10(-16) , respectively). Younger age, non-European ancestry, and anti-RNP were also independently associated with increased serum IFNα activity (P ≤ 6.7 × 10(-4) ). We found 14 unique associations between variables in network analysis, and only 7 of these associations were shared among >1 ancestral background. Associations between clinical criteria were different for different ancestral backgrounds, while autoantibody-IFNα relationships were similar across backgrounds. IFNα activity and autoantibodies were not associated with ACR clinical features in multivariate models. CONCLUSION: Our findings indicate that serum IFNα activity is strongly and consistently associated with autoantibodies, and not independently associated with clinical features in SLE. IFNα may be more relevant to humoral tolerance and initial pathogenesis than later clinical disease manifestations.

African-derived genetic polymorphisms in TNFAIP3 mediate risk for autoimmunity.

The TNF alpha-induced protein 3 (TNFAIP3) is an ubiquitin-modifying enzyme and an essential negative regulator of inflammation. Genome-wide association studies have implicated the TNFAIP3 locus in susceptibility to autoimmune disorders in European cohorts, including rheumatoid arthritis, coronary artery disease, psoriasis, celiac disease, type 1 diabetes, inflammatory bowel disease, and systemic lupus erythematosus (SLE). There are two nonsynonymous coding polymorphisms in the deubiquitinating (DUB) domain of TNFAIP3: F127C, which is in high-linkage disequilibrium with reported SLE-risk variants, and A125V, which has not been previously studied. We conducted a case-control study in African-American SLE patients using these coding variants, along with tagging polymorphisms in TNFAIP3, and identified a novel African-derived risk haplotype that is distinct from previously reported risk variants (odds ratio=1.6, p=0.006). In addition, a rare protective haplotype was defined by A125V (odds ratio=0.31, p=0.027). Although A125V was associated with protection from SLE, surprisingly the same allele was associated with increased risk of inflammatory bowel disease. We tested the functional activity of nonsynonymous coding polymorphisms within TNFAIP3, and found that the A125V coding-change variant alters the DUB activity of the protein. Finally, we used computer modeling to depict how the A125V amino acid change in TNFAIP3 may affect the three-dimensional structure of the DUB domain to a greater extent than F127C. This is the first report of an association between TNFAIP3 polymorphisms and autoimmunity in African-Americans.

Gene-expression-guided selection of candidate loci and molecular phenotype analyses enhance genetic discovery in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a highly heterogeneous autoimmune disorder characterized by differences in autoantibody profiles, serum cytokines, and clinical manifestations. We have previously conducted a case-case genome-wide association study (GWAS) of SLE patients to detect associations with autoantibody profile and serum interferon alpha (IFN-α). In this study, we used public gene expression data sets to rationally select additional single nucleotide polymorphisms (SNPs) for validation. The top 200 GWAS SNPs were searched in a database which compares genome-wide expression data to genome-wide SNP genotype data in HapMap cell lines. SNPs were chosen for validation if they were associated with differential expression of 15 or more genes at a significance of P < 9 × 10(-5). This resulted in 11 SNPs which were genotyped in 453 SLE patients and 418 matched controls. Three SNPs were associated with SLE-associated autoantibodies, and one of these SNPs was also associated with serum IFN-α (P < 4.5 × 10(-3) for all). One additional SNP was associated exclusively with serum IFN-α. Case-control analysis was insensitive to these molecular subphenotype associations. This study illustrates the use of gene expression data to rationally select candidate loci in autoimmune disease, and the utility of stratification by molecular phenotypes in the discovery of additional genetic associations in SLE.

Body image in patients with systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE), a multisystemic disease of young women may be disfiguring and affect physical and emotional health. Body image literature in SLE is scant and controversial. PURPOSE: We compared body image-related quality of life in subjects with (n = 87) and without (n = 78) SLE and determined its correlates using the body image quality of life inventory (BIQLI). METHOD: The tool was self-administered to consenting individuals. Demographic information along with disease activity and damage assessments for SLE patients were obtained. T test, chi square test, correlational, and regression analyses were used to make comparisons. RESULTS: Mean age (±SD) were 42.4 ± 13.1 and 38.7 ± 13.2 years for SLE and non-SLE subjects, respectively. Mean (±SD) BIQLI scores were significantly worse in SLE than non-SLE subjects: 19.9 ± 33.2 and 41.6 ± 24.8 (p = 0.001). In SLE, BIQLI scores correlated inversely with overall damage, irreversible cutaneous damage, alopecia, and self-reported depression, and directly with age and health status. CONCLUSION: Body image in SLE is poor, and effective interventions may be directed at cutaneous disease activity, damage, and depression.