Perceived functioning has ethnic-specific associations in systemic sclerosis: another dimension of personalized medicine.

OBJECTIVE: To measure self-reported physical and mental functioning and associated clinical features at study entry in 3 ethnic groups with systemic sclerosis (SSc). METHODS: Sixty Hispanic, 39 African American, and 104 Caucasian patients with recent-onset SSc (< 5 yrs) were assessed for perceived physical and mental functioning, using the Medical Outcomes Study Short Form-36 (SF-36) and Scleroderma-Health Assessment Questionnaire (Scleroderma-HAQ). Socioeconomic, demographic, clinical, immunologic, immunogenetic, behavioral, and psychological variables (Interpersonal Support Evaluation List, ISEL; Illness Behavior Questionnaire, IBQ; and Arthritis Helplessness Index, AHI) were analyzed by linear regression models for associations with SF-36 and mHAQ scores as dependent variables. RESULTS: Perceived physical functioning scores had ethnic-specific associations with AHI > fatigue scores > IBQ > clinical variables (hypertension, skin score, and percentage predicted DLCO). Scleroderma-HAQ scores had ethnic-specific associations with IBQ > AHI scores > most clinical and laboratory variables. Decreased mental component summary (MCS) scores associated with AHI > ISEL. Ethnic-specific immunogenetic variables HLA-DQB1*0202 (Caucasian) and HLA-DRB 1*11 (African American), and HLA-DQA1*0501 (Hispanic) also associated with MCS. Antinuclear autoantibodies, anti-topoisomerase I, and RNA polymerases I and III also demonstrated associations with functioning in African American and Hispanic groups. CONCLUSION: Clinical, psychosocial, and immunogenetic variables had ethnic-specific associations with perceived physical and mental functioning. Consideration of ethnic-specific psychological and behavioral support in designing more personalized, relevant therapeutic interventions for the patient may improve therapeutic efficacy in SSc.

Coccidioidomycosis pneumonia in a nonendemic area associated with infliximab.

Tumor necrosis factor (TNF) inhibitors, such as infliximab, are highly effective in the management of rheumatoid arthritis; however, these agents are associated with an increased risk of infectious complications. Individuals developing coccidiomycosis pneumonia frequently acquire this while residing in endemic regions. We present a patient with rheumatoid arthritis treated with infliximab who developed acute respiratory distress syndrome (ARDS) from coccidiomycosis pneumonia while residing in a non-endemic region near the Texas-Louisiana border and was successfully treated with antifungal therapy. The source for coccidiomycosis was suspected to be from inhalation of pulverized rock dust imported from Arizona. Patients treated with TNF inhibitors may acquire coccidiomycosis infection through fomite dust exposure.

Eosinophilic enteritis with systemic lupus erythematosus.

Gastrointestinal manifestations are common in systemic lupus erythematosus (SLE). Eosinophilic enteritis is a rare disorder of uncertain cause that was recently reported for the first time in association with SLE. This report presents a second case of eosinophilic enteritis in a 47-year-old female patient with SLE. The patient presented with recurrent episodes of abdominal pain, nausea, vomiting, and diarrhea. Complete blood counts on occasion showed elevated eosinophil counts. The patient underwent a comprehensive workup over several weeks, culminating in a small bowel biopsy that showed eosinophil infiltration in the muscularis propria, establishing the diagnosis. The patient was treated with a prolonged taper of prednisone with successful resolution of symptoms.

Systemic lupus erythematosus in three ethnic groups: XVI. Association of hydroxychloroquine use with reduced risk of damage accrual.

OBJECTIVE: To examine whether hydroxychloroquine (HCQ) usage is associated with a reduced risk of damage accrual in patients with systemic lupus erythematosus (SLE). METHODS: Patients (n = 518) meeting the American College of Rheumatology criteria for diagnosis of SLE and with

Systemic lupus erythematosus in a multiethnic lupus cohort (LUMINA). XVII. Predictors of self-reported health-related quality of life early in the disease course.

OBJECTIVE: To determine the baseline factors predictive of self-reported health-related quality of life (HRQOL) early in the course of systemic lupus erythematosus patients (SLE) from a multiethnic LUMINA (Lupus in Minorities: Nature versus nurture) cohort. METHODS: LUMINA patients with > or =2 visits were studied. Self-reported HRQOL was examined with the 8 subscales and 2 summary measures (the Physical Component Summary [PCS], and the Mental Component Summary [MCS]) of the Short Form 36 (SF-36). Bivariable and multivariable analyses were done with the PCS, MCS and 8 subscales as the dependent variables. The analyses were performed including and excluding the corresponding SF-36 measure from the independent variables. Age, sex, and ethnicity were included in all models. Time was modeled in all regressions. RESULTS: A total of 1,351 visits (346 patients [80 Hispanics-Texas, 34 Hispanics-Puerto Rico, 126 African Americans, and 106 Caucasians]) were included in these analyses. Mean +/- SD PCS and MCS scores were 36.7 +/- 12.0 and 46.6 +/- 11.5, respectively. The scores for the eight subscales of the SF-36 were also lower than those for the general population. Baseline SF-36 measures were highly predictive of subsequent HRQOL. In the same set of regressions, older age was found to consistently predict poor self-reported HRQOL whereas fibromyalgia, helplessness, fatigue, and abnormal illness-related behaviors were also predictive, but less consistently. Estimated adjusted variances in these regressions ranged from 23% (Role-Emotional [RE]) to 43% (Physical Functioning [PF]). CONCLUSION: In patients with SLE, poor baseline HRQOL was highly predictive of subsequent poor HRQOL. Other predictive variables of poor functioning were primarily psychological/behavioral and socioeconomic-demographic.

Systemic lupus erythematosus in three ethnic groups. XVIII. Factors predictive of poor compliance with study visits.

OBJECTIVE: To determine the baseline factors predictive of poor compliance with study visits in a longitudinal multiethnic lupus cohort study. METHODS: Patients with systemic lupus erythematosus (n = 344) representing a total of 2,069 potential study visits were studied. Of the participants, 24.4% were Hispanic, 43.3% African American, and 32.3% Caucasian. Noncompliance was defined as missing 2 or more study visits. For the purpose of these analyses, visits completed only by review of medical records were considered missing. Baseline socioeconomic-demographic, clinical, and psychosocial features between compliant and noncompliant patients were compared. Variables with P < 0.10 were then entered into a multivariable logistic regression analysis with compliance being the dependent variable. RESULTS: There were 178 compliant and 166 noncompliant patients. Noncompliant patients were more likely to be young, unmarried, of African American ethnicity, live closer to the medical centers, and have longer disease duration and greater disease activity as assessed by the physician than the compliant patients. In the multivariable model, longer disease duration (P = 0.010), higher level of disease activity (P = 0.009), and shorter distance to travel to study visits (P = 0.046) were predictors of noncompliance; their odds ratios and confidence intervals were below 1. CONCLUSIONS: We have identified baseline patient characteristics that may predict noncompliance with study visits (disease duration, disease activity, and distance to the medical center). This information will serve as the basis for developing interventions to curtail noncompliance. Our data may have applicability in other lupus cohort studies.

Systemic lupus erythematosus in three ethnic groups. XIV. Poverty, wealth, and their influence on disease activity.

OBJECTIVE: To determine the impact of wealth on disease activity in the multiethnic (Hispanic, African American, and Caucasian) LUMINA (Lupus in Minorities, Nature versus nurture) cohort of patients with systemic lupus erythematosus (SLE) and disease duration < or =5 years at enrollment. METHODS: Variables (socioeconomic, demographic, clinical, immunologic, immunogenetic, behavioral, and psychological) were measured at enrollment and annually thereafter. Four questions from the Women's Health Initiative study were used to measure wealth. Disease activity was measured with the Systemic Lupus Activity Measure (SLAM). The relationship between the different variables and wealth was then examined. Next, the impact of wealth on disease activity was examined in regression models where the dependent variables were the SLAM score and SLAM global (physician). Variables previously found to impact disease activity plus the wealth questions were included in the models. RESULTS: Questions on income, assets, and debt were found to distinguish patients into groups, wealthier and less wealthy. Less wealthy patients tended to be younger, women, noncaucasian, less educated, unmarried, less likely to have health insurance, and more likely to live below the poverty line. They also tended to have more active disease, more abnormal illness-related behaviors, less social support, and lower levels of self reported mental functioning. None of the wealth questions was retained in the regression models, although other socioeconomic features (such as African American ethnicity, poverty, and younger age) did. CONCLUSIONS: Wealth, per se, does not appear to have an additional predictive value, over and above traditional measures of socioeconomic status, in SLE disease activity.

Systemic lupus erythematosus in three ethnic groups. XI. Sources of discrepancy in perception of disease activity: a comparison of physician and patient visual analog scale scores.

OBJECTIVE: To compare patient's and physician's assessment of disease activity in a multiethnic (Hispanic, African American, and Caucasian) cohort of systemic lupus erythematosus (SLE) patients. METHODS: Three hundred patients with SLE from the LUMINA (Lupus in Minority populations: Nature versus nurture) cohort were included. Disease activity was assessed with the Systemic Lupus Activity Measure (SLAM); patients and physicians assessed disease activity using a 10-cm anchored visual analog scale (VAS). The difference between VAS scores was termed discrepancy (>1 cm was considered a priori clinically relevant). Selected sociodemographic, clinical, behavioral, and psychological variables were examined in relation to discrepancy in univariable and multivariable models adjusting for the physician global VAS score in order to eliminate ceiling and floor effects. RESULTS: A discrepancy was exhibited by 58% of the patients. Abnormal laboratory findings were negatively associated with discrepancy, and poor self-perceived functioning and joint involvement were positively associated with discrepancy. Ethnicity did not account for discrepant perception of disease activity. CONCLUSION: Patients and physicians rate disease activity in SLE differently. Physicians appear to place more emphasis on laboratory features while patients place more emphasis on function.

Systemic lupus erythematosus in three ethnic groups. X. Measuring cognitive impairment with the cognitive symptoms inventory.

OBJECTIVE: To determine the factor structure of the Cognitive Symptoms Inventory (CSI) in patients with systemic lupus erythematosus (SLE) participating in a multiethnic longitudinal study of outcome, the Lupus in Minority populations, Nature versus nurture (LUMINA) study. METHODS: LUMINA patients of Hispanic (n = 48), African American (n = 64), and Caucasian (n = 44) ethnicity who had a study visit (enrollment or followup) between January 1 and September 30, 2000 were included. Patients completed the CSI, a 21-item self-report measure of cognitive function. Sociodemographic, clinical, immunologic, psychosocial, and behavioral variables were ascertained per protocol and as previously described. Data were analyzed with SPSS. The factor structure of the CSI was determined using the principal axis method with oblique rotation as decided by Gorsuch. All factors having an Eigenvalue greater than 1 were considered. A 4-factor solution was derived that accounted for 42.6% of the common variance. The correlations between patient factor scale scores and variables from the demographic, clinical, psychosocial, and behavioral domains were then examined. RESULTS: The four factors and their respective variance are, Attention/Concentration (28.8%), Pattern Recognition/Activity Management (5.7%), Intermediate Memory (4.7%), and Initiation of Executive Functions (3.4%); each factor correlated with the total CSI score. Overall, patients' factor scale scores were positively and significantly correlated with other measures of cognitive dysfunction such as the Systemic Lupus Activity Measure (neuromotor domain) or the Systemic Lupus International Collaborating Clinics Damage Index (neurocognitive impairment), as well as with measures of fatigue, maladaptive coping skills, poor mental functioning, poor social support, and helplessness. They were, however, not correlated with sociodemographic or clinical variables. CONCLUSIONS: In addition to demonstrating that the CSI can be used to measure cognitive impairment in patients with SLE in the research setting, we have determined a 4-factor solution for the CSI that appears to have adequate metric properties. At present, the CSI may best be used as a screen for difficulties in daily activities involving intermediate memory, concentration, attention, and executive function. Nevertheless, further work with the CSI items and factor scales is necessary to establish internal and test-retest reliability of the factor scales; and provide additional evidence of the convergent and predictive validity of these scales in larger samples of patients from each ethnic subgroup.

Hydroxychloroquine concentration-response relationships in patients with rheumatoid arthritis.

OBJECTIVE: A dose-response relationship for hydroxychloroquine (HCQ), in terms of the proportion of patients achieving the Paulus 20% criteria for improvement, had previously been observed in patients with rheumatoid arthritis (RA) receiving a 6-week loading regimen of 400, 800, or 1,200 mg HCQ daily. This present retrospective analysis was performed to investigate possible relationships between the blood HCQ and HCQ-metabolite concentrations and measures of efficacy and toxicity. In addition, we sought to ascertain whether further investigation of HCQ/HCQ-metabolite levels might lead to testing of one of these substances as a new antirheumatic drug. METHODS: Patients with active RA (n = 212) began a 6-week, double-blind trial comparing 3 different doses of HCQ at 400, 800, or 1,200 mg/day, followed by 18 weeks of open-label HCQ treatment at 400 mg/day. Patients were repeatedly evaluated for treatment efficacy and toxicity. Blood samples were available from 123 patients for analysis of HCQ, desethylhydroxychloroquine (DHCQ), desethylchloroquine (DCQ), and bisdesethylchloroquine (BDCQ) levels using high-performance liquid chromatography. Achievement of the modified Paulus 20% improvement criteria for response in RA was used as the primary efficacy parameter. Spontaneously reported adverse events were categorized and analyzed as toxicity outcome variables. The relationship between response (efficacy and toxicity) and drug levels was evaluated using logistic regression analysis. RESULTS: The subset of patients with blood concentration data was equivalent to the larger study population in all demographic and outcome characteristics. The mean HCQ, DHCQ, and DCQ elimination half-lives were 123, 161, and 180 hours, respectively. There was a positive correlation between the Paulus 20% improvement criteria response and blood DHCQ concentrations during weeks 1-6 (P < 0.001). A potential relationship between ocular adverse events and BDCQ levels was found (P = 0.036). Logistic regression analysis of adverse events data showed that adverse gastrointestinal events were associated with higher HCQ levels (P = 0.001-0.021) during weeks 1, 2, and 3. CONCLUSION: There is a weak, but predictable, relationship between blood DHCQ concentrations and efficacy of treatment with HCQ. In addition, there is an association between gastrointestinal adverse events and elevated blood HCQ concentrations. Further investigation of these relationships is warranted to see if DHCQ may be introduced as a new antirheumatic drug.