Informing Digital Programs for Lupus Self-Management Education: A Systematic Scoping Review.

OBJECTIVE: We describe the characteristics, content, and effectiveness of digital self-management (SM) education programs for lupus and other chronic conditions to identify gaps and inform the improvement of future programs in lupus. METHODS: Three bibliographic databases were searched for articles published between May 2012 and April 2022. The search was cast to capture the breadth of digital SM education programs in the following conditions: lupus, epilepsy, fibromyalgia, multiple sclerosis, sickle cell anemia, Sjogren's syndrome, psoriatic arthritis, and rheumatoid arthritis. Title and abstract screening, as well as full-text review, was conducted by two independent reviewers. Data extraction was first completed by one author charting all studies and then, a second time, by four members of the research team charting collaboratively. RESULTS: Of the 1,969 articles identified through the search, 14 met inclusion criteria. Two additional articles were included following bibliography review. The 16 articles represented 12 unique digital SM education programs. Programs covered five conditions: epilepsy (n=3), fibromyalgia (n=2), multiple sclerosis (n=4), lupus (n=1), and rheumatoid arthritis (n=2). Most programs were asynchronous and internet-based (n=9) with a prescribed sequence of content (n=8). Peer, technical, or specialist support was offered in seven programs. Most programs demonstrated statistically significant improvement of symptoms in the intervention group (n=8). CONCLUSION: This scoping review summarizes the current landscape for digital SM education programs in lupus and similar conditions. In lupus, further investigation will fill in the gaps around digital SM education needs, user experience and evaluation of outcomes.

Prevalence of concomitant rheumatologic diseases and autoantibody specificities among racial and ethnic groups in SLE patients.

Objective: Leveraging the Manhattan Lupus Surveillance Program (MLSP), a population-based registry of cases of systemic lupus erythematosus (SLE) and related diseases, we investigated the proportion of SLE with concomitant rheumatic diseases, including Sjögren's disease (SjD), antiphospholipid syndrome (APLS), and fibromyalgia (FM), as well as the prevalence of autoantibodies in SLE by sex and race/ethnicity. Methods: Prevalent SLE cases fulfilled one of three sets of classification criteria. Additional rheumatic diseases were defined using modified criteria based on data available in the MLSP: SjD (anti-SSA/Ro positive and evidence of keratoconjunctivitis sicca and/or xerostomia), APLS (antiphospholipid antibody positive and evidence of a blood clot), and FM (diagnosis in the chart). Results: 1,342 patients fulfilled SLE classification criteria. Of these, SjD was identified in 147 (11.0%, 95% CI 9.2-12.7%) patients with women and non-Latino Asian patients being the most highly represented. APLS was diagnosed in 119 (8.9%, 95% CI 7.3-10.5%) patients with the highest frequency in Latino patients. FM was present in 120 (8.9%, 95% CI 7.3-10.5) patients with non-Latino White and Latino patients having the highest frequency. Anti-dsDNA antibodies were most prevalent in non-Latino Asian, Black, and Latino patients while anti-Sm antibodies showed the highest proportion in non-Latino Black and Asian patients. Anti-SSA/Ro and anti-SSB/La antibodies were most prevalent in non-Latino Asian patients and least prevalent in non-Latino White patients. Men were more likely to be anti-Sm positive. Conclusion: Data from the MLSP revealed differences among patients classified as SLE in the prevalence of concomitant rheumatic diseases and autoantibody profiles by sex and race/ethnicity underscoring comorbidities associated with SLE.

Economic insecurities and patient-reported outcomes in patients with systemic lupus erythematosus in the USA: a cross-sectional analysis of data from the California Lupus Epidemiology Study.

BACKGROUND: Social determinants of health are consistently associated with systemic lupus erythematosus (SLE) outcomes. However, social determinants of health are typically measured with conventional socioeconomic status factors such as income or education. We assessed the association of economic insecurities (ie, food, housing, health care, and financial insecurity) with patient-reported outcomes in a cohort of patients with SLE. METHODS: In this cross-sectional analysis, data were derived from the California Lupus Epidemiology Study based in the San Francisco Bay Area, CA, USA. Participants were recruited between Feb 25, 2015, and Jan 10, 2018, from rheumatology clinics. Inclusion criteria were Bay Area residency; oral fluency in English, Spanish, Cantonese, or Mandarin; 18 years or older; ability to provide informed consent; and a physician confirmed SLE diagnosis. Food, housing, health care, and financial economic insecurities were assessed by validated screening tools. Patient-reported outcomes were obtained using PROMIS, Quality of Life in Neurological Disorders (known as Neuro-QoL) Cognitive Function short form, Patient Health Questionnaire (PHQ)-8, and General Anxiety Disorder (GAD)-7 instruments. Poverty was defined as household income of 125% or less of the federal poverty limit. Lower education was defined as less than college-graduate education. The association of economic insecurities with patient-reported outcomes was assessed by multivariable linear regression models adjusting for demographics, SLE disease characteristics, and comorbidities. We tested for interactions of insecurities with poverty and education. FINDINGS: The final cohort included 252 participants. Mean age was 49·7 (SD 13·4) years, 228 (90%) of 252 were women and 24 (10%) were men. 80 (32%) individuals self-identified as Asian, 26 (10%) as Black, 101 (40%) as White, eight (3%) as mixed race, and 37 (15%) as other race; 59 (23%) self-identified as Hispanic. 135 (54%) individuals had at least one insecurity. Insecurities were highly prevalent, and more common in those with poverty and lower education. Adjusted multivariate analyses revealed that participants with any insecurity had significantly worse scores across all measured patient-reported outcomes. For physical function, no insecurity had an adjusted mean score of 48·9 (95% CI 47·5-50·3) and any insecurity had 45·7 (44·3-47·0; p=0·0017). For pain interference, no insecurity was 52·0 (50·5-53·5) and any insecurity was 54·4 (53·0-55·8; p=0·031). For fatigue, no insecurity was 50·5 (48·8-52·3) and any insecurity was 54·9 (53·3-56·5; p=0·0005). For sleep disturbance, no insecurity was 49·9 (48·3-51·6) and any insecurity was 52·9 (51·4-54·5; p=0·012). For cognitive function, no insecurity was 49·3 (47·7-50·9) and any insecurity was 45·6 (44·1-47·0; p=0·0011). For PHQ-8, no insecurity was 4·4 (3·6-5·1) and any insecurity was 6·1 (5·4-6·8; p=0·0013). For GAD-7, no insecurity was 3·3 (2·6-4·1) and any insecurity was 5·2 (4·5-5·9; p=0·0008). Individuals with more insecurities had worse patient-reported outcomes. There were no statistically significant interactions between insecurities and poverty or education. INTERPRETATION: Having any economic insecurity was associated with worse outcomes for people with SLE regardless of poverty or education. The findings of this study provide insight into the relationship between economic insecurities and SLE outcomes and underscore the need to assess whether interventions that directly address these insecurities can reduce health disparities in SLE. FUNDING: US Centers for Disease Control, Rheumatology Research Foundation, and National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Clinical and Serologic Phenotyping and Damage Indices in Patients With Systemic Lupus Erythematosus With and Without Fibromyalgia.

OBJECTIVE: Given fibromyalgia (FM) frequently co-occurs with autoimmune disease, this study was initiated to objectively evaluate FM in a multiracial/ethnic cohort of patients with systemic lupus erythematosus (SLE). METHODS: Patients with SLE were screened for FM using the 2016 FM classification criteria during an in-person rheumatologist visit. We evaluated hybrid Safety of Estrogens in Lupus National Assessment (SELENA)-SLE Disease Activity Index (SLEDAI) scores, SLE classification criteria, and Systemic Lupus International Collaborating Clinics damage index. We compared patients with and without FM and if differences were present, compared patients with FM with patients with non-FM related chronic pain. RESULTS: 316 patients with SLE completed the FM questionnaire. 55 (17.4%) met criteria for FM. The racial composition of patients with FM differed from those without FM (P = 0.023), driven by fewer Asian patients having FM. There was no difference in SLE disease duration, SELENA-SLEDAI score, or active serologies. There was more active arthritis in the FM group (16.4%) versus the non-FM group (1.9%) (P < 0.001). The Widespread Pain Index and Symptom Severity Score did not correlate with degree of SLE activity (r = -0.016; 0.107) among patients with FM or non-FM chronic pain (r = 0.009; -0.024). Regarding criteria, patients with FM had less nephritis and more malar rash. Systemic Lupus International Collaborating Clinics damage index did not differ between groups. CONCLUSION: Except for arthritis, patients with SLE with FM are not otherwise clinically or serologically distinguishable from those without FM, and Widespread Pain Index and Symptom Severity Score indices do not correlate with SLEDAI. These observations support the importance of further understanding the underlying biology of FM in SLE.

Associations between CD70 methylation of T cell DNA and age in adults with systemic lupus erythematosus and population controls: The Michigan Lupus Epidemiology & Surveillance (MILES) Program.

BACKGROUND: Environmental factors can influence epigenetic regulation, including DNA methylation, potentially contributing to systemic lupus erythematosus (SLE) development and progression. We compared methylation of the B cell costimulatory CD70 gene, in persons with lupus and controls, and characterized associations with age. RESULTS: In 297 adults with SLE and 92 controls from the Michigan Lupus Epidemiology and Surveillance (MILES) Cohort, average CD70 methylation of CD4+ T cell DNA across 10 CpG sites based on pyrosequencing of the promoter region was higher for persons with SLE compared to controls, accounting for covariates [ß = 2.3, p = 0.011]. Using Infinium MethylationEPIC array data at 18 CD70-annoted loci (CD4+ and CD8+ T cell DNA), sites within the promoter region tended to be hypomethylated in SLE, while those within the gene region were hypermethylated. In SLE but not controls, age was significantly associated with pyrosequencing-based CD70 methylation: for every year increase in age, methylation increased by 0.14 percentage points in SLE, accounting for covariates. Also within SLE, CD70 methylation approached a significantly higher level in Black persons compared to White persons (ß = 1.8, p = 0.051). CONCLUSIONS: We describe altered CD70 methylation patterns in T lymphocyte subsets in adults with SLE relative to controls, and report associations particular to SLE between methylation of this immune-relevant gene and both age and race, possibly a consequence of "weathering" or accelerated aging which may have implications for SLE pathogenesis and potential intervention strategies.

Bladder instillation patterns in a cohort of women with interstitial cystitis/bladder pain syndrome.

Purpose: To determine intravesical instillation patterns among women receiving treatment for interstitial cystitis/bladder pain syndrome (IC/BPS). Methods: Using the Veterans Affairs Informatics and Computing Infrastructure, active female users of the Veterans Affairs system with an ICD-9 diagnosis of IC/BPS (595.1) were randomly sampled. Patients were considered to have IC/BPS (by chart review) if they had two visits complaining of bladder-centric pain in the absence of positive urine culture ≥6 weeks apart or history of bladder pain with one additional visit for bladder-centric pain. We abstracted the dates of intravesical instillations for each patient. A "course" of instillations was defined as ≥1 instillations made with <21 days between visits. Results: We identified 641 women with confirmed diagnosis of IC/BPS, 78 of whom underwent a total of 344 intravesical instillations. On average each subject had 1.5 +/- 0.8 courses between October 2004-July 2016. Each course was an average of 3.1 +/- 2.6 instillations. 55% of courses consisted of one instillation. Only 22% of courses had 6 or more instillations, the number typically recommended to achieve clinical response. Each instillation within a course was an average of 9.4 +/- 4.0 days apart. Most instillations (77%) were a cocktail of two or more drugs. Conclusions: In our cohort, few women with IC/BPS received a recommended treatment course of six weekly instillations, with most receiving only one per course. Future studies are needed to determine if instillation courses were altered from the guideline due to provider practice patterns, early improvement, or poor tolerance of instillations.

Multimorbidity in systemic lupus erythematosus in a population-based cohort: the lupus Midwest network.

OBJECTIVES: To assess the prevalence and incidence of multimorbidity and the association with the SLICC/ACR damage index (SDI) among patients with systemic lupus erythematosus (SLE). METHODS: Using prevalent and incident population-based cohorts of patients with SLE and their matched comparators, we assessed 57 chronic conditions. Chronic conditions were categorized as SDI-related or SDI-unrelated. Multimorbidity was defined as the presence of 2+ chronic conditions. Multimorbidity at prevalence and incidence/index was compared between cohorts using logistic regression. Cox models were used to examine development of multimorbidity after SLE incidence. RESULTS: The prevalent cohort included 449 patients with established SLE on January 1, 2015. They were three times more likely to have multimorbidity compared with non-SLE comparators (OR 2.98, 95% CI 2.18-4.11). The incident cohort included 270 patients with new-onset SLE. At SLE incidence, patients with SLE were more likely to have multimorbidity than comparators (OR 2.27, 95% CI 1.59-3.27). After incidence, the risk of developing multimorbidity was 2-fold higher among patients with SLE than comparators (hazard ratio (HR) 2.11, 95% CI 1.59-2.80). Development of multimorbidity was higher in patients with SLE based on SDI-related (HR 2.91, 95% CI 2.17-3.88) and SDI-unrelated conditions (HR 1.73, 95% CI, 1.32-2.26). CONCLUSION: Patients with SLE have a higher burden of multimorbidity, even before the onset of the disease. The risk disparity continues after SLE classification and is also seen in a prevalent SLE cohort. Multimorbidity is driven both by SDI-related and unrelated conditions.

Medication Cost Concerns and Disparities in Patient-Reported Outcomes Among a Multiethnic Cohort of Patients With Systemic Lupus Erythematosus.

OBJECTIVE: Concerns about the affordability of medications are common in systemic lupus erythematosus (SLE), but the relationship between medication cost concerns and health outcomes is poorly understood. We assessed the association of self-reported medication cost concerns and patient-reported outcomes (PROs) in a multiethnic SLE cohort. METHODS: The California Lupus Epidemiology Study is a cohort of individuals with physician-confirmed SLE. Medication cost concerns were defined as having difficulties affording SLE medications, skipping doses, delaying refills, requesting lower-cost alternatives, purchasing medications outside the United States, or applying for patient assistance programs. Linear regression and mixed effects models assessed the cross-sectional and longitudinal association of medication cost concerns and PROs, respectively, adjusting for age, sex, race and ethnicity, income, principal insurance, immunomodulatory medications, and organ damage. RESULTS: Of 334 participants, medication cost concerns were reported by 91 (27%). Medication cost concerns were associated with worse Systemic Lupus Activity Questionnaire (SLAQ; beta coefficient [ß] 5.9, 95% CI 4.3-7.6; P < 0.001), 8-item Patient Health Questionnaire depression scale (PHQ-8; ß 2.7, 95% CI 1.4-4.0; P < 0.001), and Patient-Reported Outcomes Measurement Information System (PROMIS; ß for physical function -4.6, 95% CI -6.7 to -2.4; P < 0.001) scores after adjusting for covariates. Medication cost concerns were not associated with significant changes in PROs over 2-year follow-up. CONCLUSION: More than a quarter of participants reported at least 1 medication cost concern, which was associated with worse PROs. Our results reveal a potentially modifiable risk factor for poor outcomes rooted in the unaffordability of SLE care.

Quality-of-life impact of interstitial cystitis and other pelvic pain syndromes.

Objective: To compare health-related quality of life (HRQOL) and pelvic pain levels over time in patients with interstitial cystitis/bladder pain syndrome (IC/BPS) and those with other pelvic pain conditions (OPPC) including chronic prostatitis, dyspareunia, vaginismus, vulvodynia, and vulvar vestibulitis. Methods: We prospectively enrolled male and female patients from any Veterans Health Administration (VHA) center in the US. They completed the Genitourinary Pain Index (GUPI) quantifying urologic HRQOL and the 12-Item Short Form Survey version 2 (SF-12) quantifying general HRQOL at enrollment and 1 year later. Participants were classified by ICD diagnosis codes and confirmed by chart review to be IC/BPS or OPPC (308 and 85 patients respectively). Results: At baseline and follow-up, IC/BPS patients, on average, had worse urologic and general HRQOL than OPPC patients. IC/BPS patients demonstrated improvement in urologic HRQOL measures over the study but demonstrated no significant change in any general HRQOL measure suggesting a condition-specific impact. Patients with OPPC demonstrated similar improvements in urologic HRQOL but had deteriorating mental health and general HRQOL at follow-up suggesting a wider general HRQOL impact for these diseases. Conclusions: We found that patients with IC/BPS had worse urologic HRQOL compared to other pelvic conditions. Despite this, IC/BPS showed stable general HRQOL over time, suggesting a more condition-specific impact on HRQOL. OPPC patients showed deteriorating general HRQOL, suggesting more widespread pain symptoms in these conditions.

Cost-related prescription non-adherence and patient-reported outcomes in systemic lupus erythematosus: The Michigan Lupus Epidemiology & Surveillance program.

OBJECTIVES: Medication access and adherence play key roles in determining patient outcomes. We investigated whether cost-related non-adherence (CRNA) to prescription medications was associated with worse patient-reported outcomes in a population-based systemic lupus erythematosus (SLE) cohort. METHODS: Sociodemographic and prescription data were collected by structured interviews in 2014-2015 from patients meeting SLE criteria in the established Michigan Lupus Epidemiology & Surveillance (MILES) Cohort. We examined the associations between CRNA and potential confounders such as sociodemographics and health insurance coverage, and outcome measures of SLE activity and damage using multivariable linear regression. RESULTS: 462 SLE participants completed the study visit: 430 (93.1%) female, 208 (45%) Black, and mean age 53.3 years. 100 (21.6%) participants with SLE reported CRNA in the preceding 12 months. After adjusting for covariates, CRNA was associated with both higher levels of current SLE disease activity [SLAQ: ß coeff 2.7 (95% CI 1.3, 4.1), p < 0.001] and damage [LDIQ ß coeff 1.4 (95% CI 0.5, 2.4), p = 0.003]. Race, health insurance status, and fulfilling Fibromyalgia (FM) Survey Criteria were independently associated with both higher (worse) SLAQ and LDIQ scores; female sex was further associated with higher SLAQ scores. CONCLUSION: Patients with SLE who reported CRNA in the previous 12 months had significantly worse self-reported current disease activity and damage scores compared to those not reporting CRNA. Raising awareness and addressing barriers or concerns related to financial implications and accessibility issues in care plans may help to improve these outcomes.

2022 American College of Rheumatology Guideline for Exercise, Rehabilitation, Diet, and Additional Integrative Interventions for Rheumatoid Arthritis.

OBJECTIVE: To develop initial American College of Rheumatology (ACR) guidelines on the use of exercise, rehabilitation, diet, and additional interventions in conjunction with disease-modifying antirheumatic drugs (DMARDs) as part of an integrative management approach for people with rheumatoid arthritis (RA). METHODS: An interprofessional guideline development group constructed clinically relevant Population, Intervention, Comparator, and Outcome (PICO) questions. A literature review team then completed a systematic literature review and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the certainty of evidence. An interprofessional Voting Panel (n = 20 participants) that included 3 individuals with RA achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: The Voting Panel achieved consensus on 28 recommendations for the use of integrative interventions in conjunction with DMARDs for the management of RA. Consistent engagement in exercise received a strong recommendation. Of 27 conditional recommendations, 4 pertained to exercise, 13 to rehabilitation, 3 to diet, and 7 to additional integrative interventions. These recommendations are specific to RA management, recognizing that other medical indications and general health benefits may exist for many of these interventions. CONCLUSION: This guideline provides initial ACR recommendations on integrative interventions for the management of RA to accompany DMARD treatments. The broad range of interventions included in these recommendations illustrates the importance of an interprofessional, team-based approach to RA management. The conditional nature of most recommendations requires clinicians to engage persons with RA in shared decision-making when applying these recommendations.

2022 American College of Rheumatology Guideline for Exercise, Rehabilitation, Diet, and Additional Integrative Interventions for Rheumatoid Arthritis.

OBJECTIVE: To develop initial American College of Rheumatology (ACR) guidelines on the use of exercise, rehabilitation, diet, and additional interventions in conjunction with disease-modifying antirheumatic drugs (DMARDs) as part of an integrative management approach for people with rheumatoid arthritis (RA). METHODS: An interprofessional guideline development group constructed clinically relevant Population, Intervention, Comparator, and Outcome (PICO) questions. A literature review team then completed a systematic literature review and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the certainty of evidence. An interprofessional Voting Panel (n = 20 participants) that included 3 individuals with RA achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: The Voting Panel achieved consensus on 28 recommendations for the use of integrative interventions in conjunction with DMARDs for the management of RA. Consistent engagement in exercise received a strong recommendation. Of 27 conditional recommendations, 4 pertained to exercise, 13 to rehabilitation, 3 to diet, and 7 to additional integrative interventions. These recommendations are specific to RA management, recognizing that other medical indications and general health benefits may exist for many of these interventions. CONCLUSION: This guideline provides initial ACR recommendations on integrative interventions for the management of RA to accompany DMARD treatments. The broad range of interventions included in these recommendations illustrates the importance of an interprofessional, team-based approach to RA management. The conditional nature of most recommendations requires clinicians to engage persons with RA in shared decision-making when applying these recommendations.

Association of the anti-thyroid peroxidase antibody with chronic hand pain in older adults in the Third National Health and Nutrition Examination Survey: a cross-sectional study.

Background: Autoimmune thyroid disease (AITD) is the commonest autoimmune disease. Although viewed as a classic form of single-organ autoimmunity, AITD is increasingly associated with non-thyroid sequelae including musculoskeletal manifestations and chronic pain syndromes. However, large population-based studies are needed. Objectives: To examine the relationships between chronic hand pain and the AITD autoantibodies, anti-thyroid peroxidase antibody (TPOAb), and anti-thyroglobulin antibody (TgAb), in the Third National Health and Nutrition Examination Survey (NHANES III). Design: This is a cross-sectional study. Methods: We examined data from NHANES III on 4820 persons aged 60 years or older with respect to hand pain and its association with TPOAb and TgAb. Log-binomial regressions were fit to examine the associations between the anti-thyroid autoantibodies and hand pain. Results: Positive TPOAb was associated with a higher prevalence of hand pain than negative TPOAb [prevalence ratio (PR) = 1.158, p = 0.048] in the unadjusted model. This association was no longer significant after controlling for age, body mass index, gender, and diabetes (p = 0.313). When positive TPOAb was considered as a categorical variable with four levels, the highest quartile was associated with hand pain in the unadjusted (PR = 1.489, p = 0.005) and adjusted models (PR = 1.325, p = 0.042). There was no significant association between TgAb and hand pain when covariates were controlled for. Conclusion: TPOAb may be associated with the presence of chronic hand pain in persons aged over 60 years, especially at higher serum levels.

Health Care Utilization in Systemic Lupus Erythematosus in the Community: The Lupus Midwest Network.

OBJECTIVE: The aim of this study was to determine inpatient health care utilization in an incident cohort of patients with systemic lupus erythematosus (SLE) compared with the general population. METHODS: This was a population-based cohort study in the upper Midwest, United States. We included patients fulfilling the European League Against Rheumatism/American College of Rheumatology SLE classification criteria between 1995 and 2018. They were 1:1 age-, sex-, county-matched with individuals without SLE. All hospital admissions and emergency department (ED) visits were electronically retrieved for 1995-2020. Rates for hospital admission, length of stay, readmission, ED visits, and discharge destination were compared between groups. RESULTS: Three hundred forty-one patients with SLE and 341 comparators without SLE were included (mean age, 48.6 years at diagnosis; 79.2% female). Rates of hospitalization for patients with SLE and comparators were 29.8 and 9.9 per 100 person-years, respectively. These differences were present across sexes and age groups. Hospitalization rates were higher in patients with SLE after diagnosis and remained higher than comparators for the first 15 years of the disease. Patients with SLE were more likely than comparators to visit the ED (hazard ratio, 2.71; 95% confidence interval, 2.05-3.59). Readmission rates (32% vs. 21%, p = 0.017) were higher in patients with SLE. Length of stay and discharge destination were similar between both groups. CONCLUSION: Patients with SLE were more likely to be hospitalized and to visit the ED than individuals without SLE, highlighting important inpatient care needs. Increased hospitalization rates were observed in both male and female patients and all age groups.

Long-Term Opioid Therapy Among Patients With Systemic Lupus Erythematosus in the Community: A Lupus Midwest Network (LUMEN) Study.

OBJECTIVE: There is little information about the epidemiology and factors associated with opioid therapy in systemic lupus erythematosus (SLE). We aimed to assess the prevalence of opioid therapy and explore factors associated with long-term opioid therapy (LTOT) in patients with SLE. METHODS: Patients with SLE were matched with controls without SLE in a population-based cohort on January 1, 2015. We captured demographics, manifestations of SLE, comorbidities (ie, fibromyalgia, mood disorders, osteoarthritis, chronic low back pain [CLBP], chronic kidney disease (CKD), avascular necrosis, osteoporosis, fragility fractures, and cancer), and the Area Deprivation Index (ADI). Opioid prescription data were used to assess the prevalence of LTOT, defined as contiguous prescriptions (gaps of < 30 days between prescriptions) and receiving opioid therapy for ≥ 90 days or ≥ 10 prescriptions before the index date. RESULTS: A total of 465 patients with SLE and 465 controls without SLE were included. In total, 13% of patients with SLE and 3% of controls without SLE were receiving opioid therapy (P < 0.001), and 11% of patients with SLE were on LTOT vs 1% of controls without SLE. Among patients with SLE, acute pericarditis (odds ratio [OR] 3.92, 95% CI 1.78-8.66), fibromyalgia (OR 7.78, 95% CI 3.89-15.55), fragility fractures (OR 3.72, 95% CI 1.25-11.07), CLBP (OR 4.00, 95% CI 2.13-7.51), and mood disorders (OR 2.76, 95% CI 1.47-5.16) were associated with LTOT. We did not find an association between opioid therapy and ADI. CONCLUSION: Patients with SLE are more likely to receive LTOT than controls. Among patients with SLE, LTOT was associated with pericarditis and several comorbidities. However, LTOT was not associated with CKD despite the limited pain control options among these patients.

The association of trauma with self-reported flares and disease activity in systemic lupus erythematosus (SLE).

OBJECTIVES: Trauma has been linked to incident SLE, but its relationship with SLE disease activity is unknown. This analysis examines associations between trauma exposures and patient-reported SLE disease activity and flares. METHODS: Data were from the California Lupus Epidemiology Study (CLUES). Flares were self-reported as any flare and, of those, flares accompanied by medical care (hospitalization or physician contact). The Systemic Lupus Activity Questionnaire (SLAQ) assessed disease activity. The Brief Trauma Questionnaire (BTQ) assessed all historical trauma exposures. The Adverse Childhood Experiences (ACEs) questionnaire was available for a subset. Multivariable regression analyses (n = 252) examined whether trauma exposure was associated with flares or SLAQ controlling for age, sex, poverty, race/ethnicity, comorbidities, perceived stress, disease duration and self-reported disease damage. RESULTS: Excluding exposure to serious illness, 63.4% reported ≥1 trauma exposure. Any traumatic event, excluding illness, doubled the odds of a flare [OR 2.27 (95% CI 1.24, 4.17)] and was associated with significantly higher SLAQ scores [ß 2.31 (0.86, 3.76)]. Adjusted odds of any flare and flare with medical care were significantly elevated for those with both BTQ and ACE exposures [5.91 (2.21, 15.82) and 4.69 (1.56, 14.07), respectively]. SLAQ scores were also higher for those with both exposures [ß 5.22 (3.00, 7.44)]. CONCLUSION: In this cohort, those with a history of trauma reported more flares and greater disease activity. Identifying mechanisms of associations between trauma and disease activity and flares, as well as interventions to mitigate the effects of trauma exposures is critical, given the high rates of trauma exposures.

Causes of Death Among Individuals With Systemic Lupus Erythematosus by Race and Ethnicity: A Population-Based Study.

OBJECTIVE: Non-White populations are at higher risk of developing systemic lupus erythematosus (SLE) and have more severe outcomes, including mortality. The present study was undertaken to examine how specific causes of death vary by race and ethnicity, including Asian and Hispanic individuals. METHODS: The California Lupus Surveillance Project included SLE cases identified among residents of San Francisco County, CA during January 1, 2007 to December 31, 2009. Cases were matched to the National Death Index over a 10-year period. Logistic regression examined age-adjusted differences in causes of death by race, ethnicity, and sex. Age-standardized mortality ratios between individuals with SLE and the corresponding general population were calculated for the leading cause of death, and observed versus expected deaths were estimated. RESULTS: The study included 812 individuals of White (38%), Asian (36%), Black (20%), and mixed/other/unknown (5%) race; 15% identified as Hispanic. One hundred thirty-five deaths were recorded, with a mean ± SD age at death of 62.2 ± 15.6 years. Cardiovascular disease (CVD) was the leading cause of death overall (33%), and across all racial and ethnic groups, followed by rheumatic disease (18%) and hematologic/oncologic conditions (18%). CVD as the underlying cause of death was 3.63 times higher among SLE cases than in the general population. CVD deaths for those with SLE were nearly 4 and 6 times higher for Asian and Hispanic individuals with SLE, respectively, compared to the general population. CONCLUSION: Individuals with SLE experience a disproportionate burden of CVD mortality compared to the general population, which is magnified for Asian and Hispanic groups.

Perceived Stress and Prediction of Worse Disease Activity and Symptoms in a Multiracial, Multiethnic Systemic Lupus Erythematosus Cohort.

OBJECTIVE: Studies have suggested a potential link between traumatic experiences, psychological stress, and autoimmunity, but the impact of stress on disease activity and symptom severity in systemic lupus erythematosus (SLE) remains unclear. The present study was undertaken to examine whether increases in perceived stress independently associate with worse SLE disease outcomes over 3 years of follow-up. METHODS: Participants were drawn from the California Lupus Epidemiology Study (CLUES). Stress was measured annually using the 4-item Perceived Stress Scale (PSS). Participants with increases of ≥0.5 SD in PSS score were defined as having an increase in stress. Four outcomes were measured at the year 3 follow-up visit: physician-assessed disease activity (Systemic Lupus Erythematosus Disease Activity Index); patient-reported disease activity (Systemic Lupus Activity Questionnaire); pain (Patient-Reported Outcomes Measurement Information System [PROMIS] pain interference scale); and fatigue (PROMIS fatigue scale). Multivariable linear regression evaluated longitudinal associations of increase in stress with all 4 outcomes while controlling for potential confounders. RESULTS: The sample (n = 260) was 91% female, 36% Asian, 30% White, 22% Hispanic, and 11% African American; the mean ± SD age was 46 ± 14 years. In adjusted longitudinal analyses, increase in stress was independently associated with greater physician-assessed disease activity (P = 0.015), greater self-reported disease activity (P < 0.001), more pain (P = 0.019), and more fatigue (P < 0.001). CONCLUSION: In a racially diverse sample of individuals with SLE, those who experienced an increase in stress had significantly worse disease activity and greater symptom burden at follow-up compared to those with stress levels that remained stable or declined. Findings underscore the need for interventions to bolster stress resilience and support effective coping strategies among individuals living with lupus.

Race, Ethnicity, and Disparities in the Risk of End-Organ Lupus Manifestations Following a Systemic Lupus Erythematosus Diagnosis in a Multiethnic Cohort.

OBJECTIVE: Data on the onset of lupus manifestations across multiple organ domains and in diverse populations are limited. The objective was to analyze racial and ethnic differences in the risk of end-organ lupus manifestations following systemic lupus erythematosus (SLE) diagnosis in a multiethnic cohort. METHODS: The California Lupus Epidemiology Study (CLUES) is a longitudinal study of SLE. Data on major end-organ lupus manifestations were collected and categorized by organ system: renal, hematologic, neurologic, cardiovascular, and pulmonary. Multiorgan disease was defined as manifestations in ≥2 of these distinct organ systems. Kaplan-Meier curves assessed end-organ disease-free survival, and Cox proportional hazards regression estimated the rate of end-organ disease following SLE diagnosis, adjusting for age at diagnosis, sex, and self-reported race and ethnicity (White, Hispanic, Black, and Asian). RESULTS: Of 326 participants, 89% were female; the mean age was 45 years. Self-reported race and ethnicity were 30% White, 23% Hispanic, 11% Black, and 36% Asian. Multiorgan disease occurred in 29%. Compared to White participants, Hispanic and Asian participants had higher rates, respectively, of renal (hazard ratio [HR] 2.9 [95% confidence interval (95% CI) 1.8-4.7], HR 2.9 [95% CI 1.9-4.6]); hematologic (HR 2.7 [95% CI 1.3-5.7], HR 2.1 [95% CI 1.0-4.2]); and multiorgan disease (HR 3.3 [95% CI 1.8-5.9], HR 2.5 [95% CI 1.4-4.4]) following SLE diagnosis. CONCLUSION: We found heightened risks of developing renal, hematologic, and multiorgan disease following SLE diagnosis among Hispanic and Asian patients with SLE, as well as a high burden of multiorgan disease among CLUES participants.

Food Sensitivities in a Diverse Nationwide Cohort of Veterans With Interstitial Cystitis/Bladder Pain Syndrome.

PURPOSE: Prior studies suggest that certain foods exacerbate interstitial cystitis/bladder pain syndrome symptoms. However, these studies were limited in size and demographics. We assessed the presence of diet sensitivities among patients with interstitial cystitis/bladder pain syndrome and compared them with patients with other pelvic pain conditions and healthy controls. MATERIALS AND METHODS: We identified Veterans Affairs patients nationwide by querying ICD-9/10 codes for interstitial cystitis/bladder pain syndrome. Patients were assigned to interstitial cystitis, other pelvic pain, or healthy control cohorts after chart review. We mailed all patients the Shorter-Moldwin Food Sensitivity Questionnaire to evaluate the self-perceived effects of specific foods/beverages on urinary symptoms and/or bladder pain. RESULTS: In the interstitial cystitis/bladder pain syndrome cohort, 70% had ≥1 food sensitivity vs 37% of the other pelvic pain cohort and 32% of healthy controls (P < .001). The average number of sensitivities were similar between other pelvic pain conditions and healthy control cohorts, which were significantly less than in interstitial cystitis/bladder pain syndrome patients. Interstitial cystitis/bladder pain syndrome patients were more sensitive to acidic, spicy foods, and certain beverages vs other cohorts (all P < .001). Within the interstitial cystitis/bladder pain syndrome cohort, Black patients had significantly higher sensitivity to alcoholic and noncaffeinated beverages than Whites. Black patients did report significantly worsened urinary urgency than Whites (P < .05). CONCLUSIONS: In a diverse population of veterans, interstitial cystitis/bladder pain syndrome patients had significantly more food sensitivities than those without interstitial cystitis/bladder pain syndrome. This suggests that food sensitivities could be suggestive of interstitial cystitis/bladder pain syndrome, which could make the Shorter-Moldwin Food Sensitivity Questionnaire a helpful diagnostic tool and aid in distinguishing interstitial cystitis/bladder pain syndrome from conditions often confused with interstitial cystitis/bladder pain syndrome.