Breast cancer in systemic lupus erythematosus.

OBJECTIVE: Evidence points to a decreased breast cancer risk in systemic lupus erythematosus (SLE). We analyzed data from a large multisite SLE cohort, linked to cancer registries. METHODS: Information on age, SLE duration, cancer date, and histology was available. We analyzed information on histological type and performed multivariate logistic regression analyses of histological types according to age, SLE duration, and calendar year. RESULTS: We studied 180 breast cancers in the SLE cohort. Of the 155 cases with histology information, 11 were referred to simply as 'carcinoma not otherwise specified'. In the remaining 144 breast cancers, the most common histological type was ductal carcinoma (n = 95; 66%) followed by lobular adenocarcinoma (n = 11; 8%), 15 cancers were of mixed histology, and the remaining ones were special types. In our regression analyses, the independent risk factors for lobular versus ductal carcinoma was age [odds ratio (OR) 1.07, 95% confidence interval (CI) 1.01-1.14] and for the 'special' subtypes it was age (OR 1.06, 95% CI 1.01-1.10) and SLE duration (OR 1.05, 95% CI 1.00-1.11). CONCLUSIONS: Generally, up to 80% of breast cancers are ductal carcinomas. Though our results are not definitive, in the breast cancers that occur in SLE, there may be a slight decrease in the ductal histological type. In our analyses, age and SLE duration were independent predictors of histological status.

The relationship between cancer and medication exposures in systemic lupus erythaematosus: a case-cohort study.

OBJECTIVE: To examine if, in systemic lupus erythaematosus (SLE), exposure to immunosuppressive therapy (cyclophosphamide, azathioprine, methotrexate) increases cancer risk. METHODS: A case-cohort study was performed within a multi-site international SLE cohort; subjects were linked to regional tumour registries to determine cancer cases occurring after entry into the cohort. We calculated the hazard ratio (HR) for cancer after exposure to an immunosuppressive drug, in models that controlled for other medications (anti-malarial drugs, systemic glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin), smoking, age, sex, race/ethnicity, geographic location, calendar year, SLE duration, and lupus damage scores. In the primary analyses, exposures were treated categorically (ever/never) and as time-dependent. RESULTS: Results are presented from 246 cancer cases and 538 controls without cancer. The adjusted HR for overall cancer risk after any immunosuppressive drug was 0.82 (95% CI 0.50-1.36). Age > or = 65, and the presence of non-malignancy damage were associated with overall cancer risk. For lung cancer (n = 35 cases), smoking was also a prominent risk factor. When looking at haematological cancers specifically (n = 46 cases), there was a suggestion of an increased risk after immunosuppressive drug exposures, particularly when these were lagged by a period of 5 years (adjusted HR 2.29, 95% CI 1.02-5.15). CONCLUSIONS: In our SLE sample, age > or = 65, damage, and tobacco exposure were associated with cancer risk. Though immunosuppressive therapy may not be the principal driving factor for overall cancer risk, it may contribute to an increased risk of haematological malignancies. Future studies are in progress to evaluate independent influence of medication exposures and disease activity on risk of malignancy.

Mortality in systemic lupus erythematosus.

OBJECTIVE: To examine mortality rates in the largest systemic lupus erythematosus (SLE) cohort ever assembled. METHODS: Our sample was a multisite international SLE cohort (23 centers, 9,547 patients). Deaths were ascertained by vital statistics registry linkage. Standardized mortality ratio (SMR; ratio of deaths observed to deaths expected) estimates were calculated for all deaths and by cause. The effects of sex, age, SLE duration, race, and calendar-year periods were determined. RESULTS: The overall SMR was 2.4 (95% confidence interval 2.3-2.5). Particularly high mortality was seen for circulatory disease, infections, renal disease, non-Hodgkin's lymphoma, and lung cancer. The highest SMR estimates were seen in patient groups characterized by female sex, younger age, SLE duration <1 year, or black/African American race. There was a dramatic decrease in total SMR estimates across calendar-year periods, which was demonstrable for specific causes including death due to infections and death due to renal disorders. However, the SMR due to circulatory diseases tended to increase slightly from the 1970s to the year 2001. CONCLUSION: Our data from a very large multicenter international cohort emphasize what has been demonstrated previously in smaller samples. These results highlight the increased mortality rate in SLE patients compared with the general population, and they suggest particular risk associated with female sex, younger age, shorter SLE duration, and black/African American race. The risk for certain types of deaths, primarily related to lupus activity (such as renal disease), has decreased over time, while the risk for deaths due to circulatory disease does not appear to have diminished.

Mortality related to cerebrovascular disease in systemic lupus erythematosus.

The objective of this study was to examine mortality rates related to cerebrovascular disease in systemic lupus erythematosus (SLE) compared to the general population. Our sample was a multisite Canadian SLE cohort (10 centres, n = 2688 patients). Deaths due to cerebrovascular disease were ascertained by vital statistics registry linkage using ICD diagnostic codes. Standardized mortality ratio (SMR, ratio of deaths observed to expected) estimates were calculated. The total SMR for death due to cerebrovascular disease was 2.0 (95% confidence interval [CI] 1.0, 3.7). When considering specific types of events, the category with the greatest increased risk was that of ill-defined cerebrovascular events (SMR 44.9 95% CI 9.3, 131.3) and other cerebrovascular disease (SMR 8.4, 95% CI 2.3, 21.6). Deaths due to cerebral infarctions appeared to be less common than hemorrhages and other types of cerebrovascular events. Our data suggest an increase in mortality related to cerebrovascular disease in SLE patients compared to the general population. The large increase in ill-defined cerebrovascular events may represent cases of cerebral vasculitis or other rare forms of nervous system disease; alternately, it may reflect diagnostic uncertainty regarding the etiology of some clinical presentations in SLE patients. The suggestion that more deaths are attributed to cerebral hemorrhage, as opposed to infarction, indicates that inherent or iatrogenic factors (eg, thrombocytopenia or anticoagulation) may be important. In view of the paucity of large-scale studies of mortality attributed to neuropsychiatric outcomes in SLE, our findings highlight the need for additional research in large SLE cohorts.

Non-Hodgkin's lymphoma in systemic lupus erythematosus.

BACKGROUND: Recent evidence supports an association between systemic lupus erythematosus (SLE) and non-Hodgkin's lymphoma (NHL). OBJECTIVES: To describe demographic factors, subtypes, and survival of patients with SLE who develop NHL. METHODS: A multi-site cohort of 9547 subjects with definite SLE was assembled. Subjects at each centre were linked to regional tumour registries to determine cancer cases occurring after SLE diagnosis. For the NHL cases ascertained, descriptive statistics were calculated, and NHL subtype frequency and median survival time of patients determined. RESULTS: 42 cases of NHL occurred in the patients with SLE during the 76,948 patient-years of observation. The median age of patients at NHL diagnosis was 57 years. Thirty six (86%) of the 42 patients developing NHL were women, reflecting the female predominance of the cohort. In the patients, aggressive histological subtypes appeared to predominate, with the most commonly identified NHL subtype being diffuse large B cell (11 out of 21 cases for which histological subtype was available). Twenty two of the patients had died a median of 1.2 years after lymphoma diagnosis. CONCLUSIONS: These data suggest aggressive disease in patients with SLE who develop NHL. Continuing work should provide further insight into the patterns of presentation, prognosis, and aetiology of NHL in SLE.

An international cohort study of cancer in systemic lupus erythematosus.

OBJECTIVE: There is increasing evidence in support of an association between systemic lupus erythematosus (SLE) and malignancy, but in earlier studies the association could not be quantified precisely. The present study was undertaken to ascertain the incidence of cancer in SLE patients, compared with that in the general population. METHODS: We assembled a multisite (23 centers) international cohort of patients diagnosed as having SLE. Patients at each center were linked to regional tumor registries to determine cancer occurrence. Standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected cancers. Cancers expected were determined by multiplying person-years in the cohort by the geographically matched age, sex, and calendar year-specific cancer rates, and summing over all person-years. RESULTS: The 9,547 patients from 23 centers were observed for a total of 76,948 patient-years, with an average followup of 8 years. Within the observation interval, 431 cancers occurred. The data confirmed an increased risk of cancer among patients with SLE. For all cancers combined, the SIR estimate was 1.15 (95% confidence interval [95% CI] 1.05-1.27), for all hematologic malignancies, it was 2.75 (95% CI 2.13-3.49), and for non-Hodgkin's lymphoma, it was 3.64 (95% CI 2.63-4.93). The data also suggested an increased risk of lung cancer (SIR 1.37; 95% CI 1.05-1.76), and hepatobiliary cancer (SIR 2.60; 95% CI 1.25, 4.78). CONCLUSION: These results support the notion of an association between SLE and cancer and more precisely define the risk of non-Hodgkin's lymphoma in SLE. It is not yet known whether this association is mediated by genetic factors or exogenous exposures.

Living with lupus: a prospective pan-Canadian study.

OBJECTIVE: To portray life with lupus for women affected by this disease and to identify predictors of fatigue, a common symptom that compromises patients' quality of life. METHODS: A sample of 120 female patients (mean age 42.5 yrs) with systemic lupus erythematosus (SLE) from 9 rheumatology clinics across Canada were followed prospectively for 15 months. Assessments of psychosocial functioning took place at baseline, and at 3, 9, and 15 months. Physician examinations were conducted at baseline and 15 months. RESULTS: Significant time effects were found for: global psychological distress (p < 0.001), stress (p < 0.01), emotion-oriented coping (p < 0.001), physical health status (p < 0.001), and fatigue (p < 0.001), indicating that patients improved from baseline to 15 months. Disease activity worsened for 40.3%, improved for 50.8%, and remained the same for 8.8% of the patients from baseline to 15 months. Controlling for baseline disease activity and fatigue, and considering sleep problems, decreases in stress and depression predicted less fatigue at 15 months (p < 0.001; adjusted R2 = 0.43). CONCLUSION: Despite fluctuations in disease activity, patients with SLE, as a group, cope adequately with their disease over time. There is, nonetheless, a subset of patients (about 40%) who remain distressed and who may benefit from psychosocial interventions.

Structure of lifestyle disruptions in chronic disease: a confirmatory factor analysis of the Illness Intrusiveness Ratings Scale.

BACKGROUND: The Illness Intrusiveness Ratings Scale (IIRS) measures the extent to which disease or its treatment or both interfere with activities in important life domains. Before comparing IIRS scores within or across groups it is crucial to determine whether a common underlying factor structure exists across patient populations. OBJECTIVE: To investigate the factor structure underlying the IIRS and evaluate its stability across diagnoses. METHODS: IIRS responses from 5,671 respondents were pooled from 15 separate studies concerning quality of life in eight patient groups: rheumatoid arthritis; osteoarthritis; systemic lupus erythematosus; multiple sclerosis; end-stage renal disease (maintenance dialysis); renal transplantation; heart, liver, and lung transplantation; and insomnia. Data were gathered by different methods (eg, interview, self-administered, mail survey) and in diverse contexts (eg, individual vs. group). RESULTS: Exploratory maximum-likelihood factor analysis identified three underlying factors in a randomly selected subset of respondents (n = 400), corresponding to "Relationships and Personal Development," "Intimacy," and "Instrumental" life domains. Confirmatory factor analysis corroborated the stability of this structure in an independent subsample (n = 2100). Complementary goodness-of-fit indices confirmed the consistency of the three-factor solution, corroborating that IIRS scores are uniquely defined across patient populations. Coefficient alpha was high for total and subscale scores. CONCLUSIONS: IIRS scores can be compared meaningfully within and across patient groups. Both total and subscale scores can be used depending on research objectives.

How important is patient self-management?

This chapter addresses the issues associated with self-management in arthritis care. Alternative approaches to traditional medical care have gained popularity in the past decade. Some of the factors that have led to this are discussed in this chapter, including personal self-determination, the patient as consumer in a global economy, the backlash against medical technology, and fundamental questions about the medical model of care. Following this introduction, the goals of the Arthritis Self-Management and Bone-up on Arthritis Programs are outlined, along with the major theoretical underpinnings of both programmes. The impact of self-management programmes on the outcomes of disability, pain, depression and fatigue are reviewed, as are the potential implications for both the direct and indirect cost savings for a health system and society. The potential negative effects of self-management programmes are considered, and issues related to implementation, dissemination, quality control and long-term maintenance are reviewed. Finally, the value of self-management as a tool to be used effectively by the person with arthritis, in conjunction with his or her rheumatologist, is outlined. The relevance of well-established, valid and reliable self-management programmes is underscored by the growing number of people who seek help over the Internet. Without guidance, information can become harmful or distracting rather than helpful.

Illness intrusiveness explains race-related quality-of-life differences among women with systemic lupus erythematosus.

Our objective was to investigate whether quality of life in systemic lupus erythematosus (SLE) differs across ethnoracial groups and to identify factors that may explain race-related differences. Self-administered questionnaire data from 335 White, 40 Black, and 30 Asian women with SLE were obtained from a multi-center database. Measures assessed illness intrusiveness, psychological well-being, depressive symptoms, musculoskeletal pain, and learned helplessness. Extent of SLE disease activity was indexed by self-reported functional-system involvement. Educational attainment was indicated by number of years in school. Principal-components analysis reduced the four psychosocial measures to a single factor score. This represented psychosocial well-being In path analysis. Psychosocial well-being differed significantly across the three groups, with Whites reporting the highest, and Blacks the lowest, levels. Path analysis indicated that illness intrusiveness accounted for this race-related difference. Although disease activity was significantly associated with psychosocial well-being, it did not differ across ethnoracial groups. Illness intrusiveness and educational attainment emerged as independent mediators of the race-related difference in psychosocial well-being. We conclude that race-related quality-of-life differences exist among women with SLE and are mediated independently by illness intrusiveness and educational attainment.

ASE-1: an autoantigen in systemic lupus erythematosus.

ASE-1 is a 55 kDa nucleolar autoantigen. We show that autoantibodies to this antigen occur at a higher frequency in the sera of patients with SLE than in other systemic rheumatic diseases and that the specificity of ASE-1 as a serum marker of SLE increases as the number of epitopes recognized by the sera increases. Autoantibodies to ASE-1 were temporally associated with autoantibodies to HsEg5 but were not found in conjunction with other known serum markers of SLE. The frequency of antibodies to ASE-1 epitopes in a SLE cohort was approximately the same as anti-dsDNA. However, anti-dsDNA is associated with renal involvement, whereas ASE-1 reactivity shows an association with a history of serositis. We conclude that ASE-1 is correlated with serositis and that ASE-1 should be added to a list of autoantigens that are considered important serological features of SLE.

World wide web: opportunities, challenges, and threats.

The Internet provides new opportunities to gather information on the population and may provide alternatives to the traditional methods of conducting clinical trials in systemic lupus erythematosus. The 'world wide web-www' has grown extensively in the past decade and it is estimated that there will be over 1 billion individuals on the net by the year 2005. Notifying, recruiting and assessing patients using Internet technology are already potential uses of this electronic medium. However, total reliance on the Internet could lead to biased sampling of patients with lupus. Women with low incomes or who are unemployed are less likely to have access to the Internet. Individuals with neurological deficits may have trouble using the Internet effectively. Data collected on the web may not have high reliability and much work needs to be completed to determine the psychometric properties of information derived from this source. One of the greatest threats to contend with is protecting the confidentiality of patient information when using electronic communication. Safeguards against inadvertent or unintended release of information must receive high priority in any attempt to use the Internet for clinical trials. Particular attention should be paid to email messages, which have the potential to be intercepted or sent to individuals without clearance to see patient information. Nevertheless, the costs to systems performance caused by security measures must also be considered and balanced against the need for access by those with appropriate authority. A number of websites already exist for the benefit of patients and providers. Clinicians and scientists interested in the field of lupus research will need to keep up to date on the rapidly proliferating information that is becoming available. This article lists sites which can be visited now.

Improving medication adherence through patient education distinguishing between appropriate and inappropriate utilization. Patient Education Study Group.

OBJECTIVE: To evaluate the effectiveness of a computer assisted educational intervention to facilitate appropriate utilization of an antiinflammatory medication (Arthrotec) and investigate the mechanism by which it produces these effects. METHODS: A double blind, multicenter, randomized, controlled trial studied patients over age 50 years with hip or knee osteoarthritis (OA). All patients (n = 252) were treated with the medication (diclofenac + misoprostol). Patients randomized to the experimental group interacted with a computer program delivering information about their disease, the medication, its intended and side effects, appropriate utilization (distinguishing between appropriate versus inappropriate continuation and discontinuation of medication), patient involvement in treatment related decision making, and communication with service providers. In the control condition, another computer program presented generic information about OA. Data were collected at pre-test, post-test, and 8 week followup. RESULTS: Appropriate utilization of the medication occurred more frequently in the experimental than the control group (p<0.029). Compared to controls, the experimental group demonstrated significant improvements in knowledge, realistic expectations of drug benefits, perceived ease of adherence, and self-efficacy (all p<0.05). There was no difference between the groups with regard to illness intrusiveness, pain, or disability, but there was a greater improvement in stiffness in the experimental group (-0.63; 95% CI -0.81 to -0.45) compared to the control group (-0.39; 95% CI -0.53 to -0.25) at a level of p = 0.04. CONCLUSION: In conditions such as OA, where patient involvement in decision making is essential to the effectiveness of care, computer assisted education focussing on appropriate vs inappropriate continuation and discontinuation of medications has the potential to improve knowledge, increase self-efficacy, maintain realistic expectations, and facilitate adherence, resulting in more beneficial clinical outcomes.

Randomized clinical trials and longitudinal observational studies in systemic lupus erythematosus: consensus on a preliminary core set of outcome domains.

The OMERACT module on systemic lupus erythematosus (SLE) dealt with the definition of preliminary core sets of outcome domains for randomized clinical trials (RCT) and longitudinal observational studies (LOS). After lectures introducing the problems and addressing the key issues, 6 discussion groups, 3 each for LOS and RCT, discussed and weighted more than a dozen possible items for use as outcome domains. The means of the respective 3 groups were calculated. For both RCT and LOS the same outcome domains received more than 10 of a total maximum of 100 points: disease activity, health related quality of life (HRQOL), damage, and toxicity/adverse events. However, the weights for HRQOL and damage were different for LOS and RCT. A final vote led to the acceptance of these 4 variables as a preliminary core set for outcome in SLE by more than 80% of the participants. This core set will allow for improved design, performance, and evaluation of future studies in SLE. However, a number of domains not included in the core set were regarded as important for further analysis and research.

Quality of life in systemic lupus erythematosus patients during more and less active disease states: differential contributors to mental and physical health.

OBJECTIVE: To identify determinants of mental and physical health as a function of disease state in patients with systemic lupus erythematosus (SLE). METHODS: A sample of 129 SLE patients (mean age 42.01 years; SD 11.09) was recruited from 9 immunology/rheumatology clinics across Canada. Patients completed questionnaires assessing psychological distress, social support, coping, stress, and health-related quality of life. Physicians rated disease activity (using the revised Systemic Lupus Activity Measure; SLAM-R) and damage (using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index). Mental and physical health composite scores were derived from the Medical Outcomes Study Short Form 36. Patients were subdivided into more active (SLAM-R > or = 10; n = 38) or less active disease states (n = 91). RESULTS: Better mental health was predicted by more education and less emotion-oriented coping in the patients in a more active disease state (P = 0.0001; R2 = 0.46). Better mental health was predicted by less stress, less emotion-oriented coping and more task-oriented coping in patients during a less active disease state (P = 0.0001; R2 = 0.45). Better physical health was predicted by more emotion-oriented coping in patients in a more active disease state (P = 0.04; R2 = 0.11). Better physical health was predicted by less stress and younger age in patients during a less active disease state (P = 0.0001; R2 = 0.20). CONCLUSION: The positive association between emotion-oriented coping and better physical health in patients during a more active disease state suggests that this style of coping may be more adaptive in situations that are considered uncontrollable (e.g., SLE flare). Predictors of mental health were similar to those found in the literature, especially for SLE patients in a less active disease state.