Markedly increased incidence of critical illness in adults with Type 1 diabetes.

AIMS: To compare the incidence of and mortality after intensive care unit admission in adults with paediatric-onset Type 1 diabetes vs the general population. METHODS: Using population-based administrative data from Manitoba, Canada, we identified 814 cases of paediatric-onset Type 1 diabetes, and 3579 general population controls matched on age, sex and region of residence. We estimated the incidence of intensive care unit admission in adulthood, and compared the findings between populations using incidence rate ratios and multivariable Cox proportional hazards regression, adjusting for age, sex, comorbidity and socio-economic status. We estimated age- and sex-standardized mortality rates after intensive care unit admission. RESULTS: Between January 2000 and October 2009, the average annual incidence of intensive care unit admission among prevalent cohorts was 910 per 100 000 in the Type 1 diabetes population, and 106 per 100 000 in matched controls, an eightfold increased risk (incidence rate ratio 8.6; 95% CI 5.5, 14.0). The adjusted risk of intensive care unit admission was elevated to a greater extent among women with Type 1 diabetes compared with matched women (hazard ratio 14.7; 95% CI 7.2, 29.4) than among men with Type 1 diabetes compared with matched men (hazard ratio 4.92; 95% CI 10.3, 2.36) The most common reasons for admission in the diabetes cohort were diabetic ketoacidosis, infection and ischaemic heart disease. At 30%, 5-year mortality was higher in the diabetes cohort than in the matched cohort (relative risk 5.7; 95% CI 1.2, 8.9). CONCLUSIONS: Compared with the general population, the risk of intensive care unit admission was higher in adults with paediatric-onset Type 1 diabetes, and mortality after admission was also higher.

The prevalence and determinants of anti-DFS70 autoantibodies in an international inception cohort of systemic lupus erythematosus patients.

Autoantibodies to dense fine speckles 70 (DFS70) are purported to rule out the diagnosis of SLE when they occur in the absence of other SLE-related autoantibodies. This study is the first to report the prevalence of anti-DFS70 in an early, multinational inception SLE cohort and examine demographic, clinical, and autoantibody associations. Patients were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. The association between anti-DFS70 and multiple parameters in 1137 patients was assessed using univariate and multivariate logistic regression. The frequency of anti-DFS70 was 7.1% (95% CI: 5.7-8.8%), while only 1.1% (95% CI: 0.6-1.9%) were monospecific for anti-DFS70. In multivariate analysis, patients with musculoskeletal activity (Odds Ratio (OR) 1.24 [95% CI: 1.10, 1.41]) or with anti-ß2 glycoprotein 1 (OR 2.17 [95% CI: 1.22, 3.87]) were more likely and patients with anti-dsDNA (OR 0.53 [95% CI: 0.31, 0.92]) or anti-SSB/La (OR 0.25 [95% CI: 0.08, 0.81]) were less likely to have anti-DFS70. In this study, the prevalence of anti-DFS70 was higher than the range previously published for adult SLE (7.1 versus 0-2.8%) and was associated with musculoskeletal activity and anti-ß2 glycoprotein 1 autoantibodies. However, 'monospecific' anti-DFS70 autoantibodies were rare (1.1%) and therefore may be helpful to discriminate between ANA-positive healthy individuals and SLE.

The frequency of and associations with hospitalization secondary to lupus flares from the 1000 Faces of Lupus Canadian cohort.

OBJECTIVES: Hospitalization is a major factor in health care costs and a surrogate for worse outcomes in chronic disease. The aim of this study was to determine the frequency of hospitalization secondary to lupus flare, the causes of hospitalization, and to determine risk factors for hospitalization in patients with systemic lupus erythematosus (SLE). METHODS: Data were collected as part of the 1000 Canadian Faces of Lupus, a prospective cohort study, where annual major lupus flares including hospitalizations were recorded over a 3-year period. RESULTS: Of 665 patients with available hospitalization histories, 68 reported hospitalization related to a SLE flare over 3 years of follow-up. The average annual hospitalization rate was 7.6% (range 6.6-8.9%). The most common reasons for hospitalization were: hematologic (22.1%), serositis (20.6%), musculoskeletal (MSK) (16.2%), and renal (14.7%). Univariate risk factors for lupus hospitalization included (OR [95% CI]; p < 0.05): juvenile-onset lupus (2.2 [1.1-4.7]), number of ACR SLE criteria (1.4 [1.1-1.7], baseline body mass index (BMI) (1.1 [1.0-1.1]), psychosis (3.4 [1.2-9.9]), aboriginal race (3.2 [1.5-6.7]), anti-Smith (2.6 [1.2-5.4]), erythrocyte sedimentation rate >25 mm/hr (1.9 [1.1-3.4]), proteinuria >0.5 g/d (4.2 [1.9-9.3], and SLAM-2 score (1.1 [1.0-1.2]). After multivariate regression only BMI, number of ACR criteria, and psychosis were associated with hospitalization for lupus flare. CONCLUSIONS: The mean annual rate of hospitalization attributed to lupus was lower than expected. Hematologic, serositis, MSK and renal were the most common reasons. In a regression model elevated BMI, more ACR criteria and psychosis were associated with hospitalization.

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.

Evaluating systemic lupus erythematosus patients for lung involvement.

INTRODUCTION: We set out to determine the frequency of respiratory symptoms, abnormal lung function, and shrinking lung syndrome (SLS) among patients with systemic lupus erythematosus (SLE) and to determine correlates of SLS. METHODS: Consecutive adult patients who fulfilled the American College of Rheumatology classification criteria for SLE were enrolled. Demographics, clinical, and serologic characteristics were recorded; all patients underwent pulmonary function tests (PFT) and had either a chest X-ray or computed tomography scan. SLS was defined as dyspnea with restrictive lung physiology (defined as a forced vital capacity (FVC) <80% predicted in the absence of obstruction) who did not have any evidence of interstitial lung disease on chest imaging; controls were symptomatic patients with no restrictive physiology and the absence of interstitial changes on chest imaging. RESULTS: Sixty-nine out of 110 (63%) patients had respiratory symptoms, 73 (66%) patients had abnormal lung function, and 11 (10%) patients met the definition for SLS. In a multivariate model controlling for disease duration, a history of pleuritis, modified American College of Rheumatology total score, seropositivity for dsDNA and RNP antibodies, increased disease duration (odds ratio (OR) = 1.2; 95% confidence interval (CI) of 1.0-1.3, p = 0.04), seropositivity for anti-RNP (OR = 24.4; 95% CI of 1.6-384.0, p = 0.02), and a history of serositis were significantly associated with SLS when compared with symptomatic controls. CONCLUSION: Respiratory symptoms, abnormal lung function, and SLS are common in SLE. Clinicians should consider evaluation for SLS among symptomatic patients with long-standing disease and a history of pleuritis.

Sm antibodies increase risk of death in systemic lupus erythematosus.

The importance of ethnicity, socioeconomic status (SES), and autoantibodies as prognostic indicators in lupus were evaluated in a Canadian cohort. A retrospective review of 330 lupus patients identified demographic features including age and self reported ethnicity, SES, lupus features, antibodies to extractable nuclear antigens (ENAs), organ damage (SDI score), and mortality. ENA (Sm, RNP, Ro, La) associations with lupus features, predictors of final visit SDI score and the contributions of ethnicity, autoantibodies and SES on overall mortality were determined. Three ethnic groups [Caucasians (C), Asian-Orientals (AO), Native American First Nations (FN)] differed in disease severity and SES. FN and AO patients had similarly severe lupus, developing lupus at an earlier age, with more renal and neurological involvement, greater SDI scores at last visit, and more frequently had Sm or RNP antibodies than C. FN had the highest mortality and lowest SES. Sm and RNP antibodies were associated with renal and neurologic involvement. RNP, education and duration of follow-up predicted SDI score. Sm increased risk of death. In conclusion, RNP and lower SES are associated with lupus related organ damage and the presence of Sm is a predictor of mortality in lupus, independent of ethnicity, renal involvement or socioeconomic status.

Systemic lupus erythematosus in North American Indians: a population based study.

OBJECTIVE: To evaluate the prevalence, disease course, and survival of patients with systemic lupus erythematosus (SLE) in a population of over 120,000 North American Indians (NAI), and contrast the results to those in the non-Indian population. METHODS: The regional arthritis center database and the medical records of all rheumatologists, hematologists, nephrologists, and general internists with > 1 patient with SLE were searched for cases of SLE diagnosed between 1980 and 1996. A random survey of 20% of family physicians serving this population suggested that > 85% of all SLE cases were identified. Demographics, SLE Disease Activity Index (SLEDAI) scores, Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage scores. clinical manifestations, and therapy for NAI were contrasted with the results in Caucasians (CAUC). RESULTS: We identified 257 cases meeting the ACR criteria for SLE diagnosed between 1980 and 1996. There were 49 NAI cases, resulting in a prevalence of 42.3/100,000, compared to a prevalence of 20.6/100,000 for the remainder of the population. NAI patients were younger at diagnosis, had higher SLEDAI scores at diagnosis, and had more frequent vasculitis, proteinuria and cellular casts. There were no treatment differences at diagnosis or at 2 years, but NAI patients were significantly more likely to receive treatment with prednisone or immunosuppressives at the last clinic visit. The NAI patients had similar damage scores at diagnosis, but significantly higher scores at 2 years and at the last clinic visit. NAI ethnicity increased the likelihood of death more than 4-fold. CONCLUSION: The prevalence of SLE was increased 2-fold in the NAI population. NAI patients had higher SLEDAI scores at diagnosis and more frequent vasculitis and renal involvement, required more treatment later in the disease course, accumulated more damage following diagnosis, and had increased fatality.

Rheumatic diseases in North America's indigenous peoples.

OBJECTIVES: There are at least 3 million North American Indians and Eskimos in North America. The epidemiology of rheumatic diseases in Native North Americans differs from that described for the remainder of the North American population. An enhanced understanding of rheumatic diseases in these indigenous people may provide valuable clues to the cause of these disorders and improve rheumatologic care. METHODS: The world literature was searched for all reports of rheumatic diseases in North American Indians and Eskimos. The reports were reviewed and the findings summarized by disease process. RESULTS: Many Native American groups have high prevalence rates of rheumatoid arthritis (RA), systemic lupus erythematosus, connective tissue diseases, and spondyloarthropathies. There appears to be a correlation between the pattern of rheumatic diseases in Native North Americans and the patterns of migration and ancestry. In general, Amerind Indians have increased rates of RA and connective tissue disease, while Na-Dene Indians and Eskimos have high rates of spondyloarthropathies. The RA seen in Native Americans is generally severe, seropositive, with an early age of onset, and frequent extraarticular manifestations. Many Native American groups have very high frequencies of the RA shared epitope. The majority of Native American and Eskimo groups also have high frequencies of HLA-B27, and some of the world's highest prevalence rates of spondyloarthropathies are described in these groups. Although some groups show a marked tendency to develop either Reiter's syndrome or ankylosing spondylitis, psoriatic and enteropathic arthritis are rare. CONCLUSIONS: The excess rheumatic disease seen in this population is most likely genetic in origin. Because of the combination of high rates of rheumatic disease and relative genetic homogeneity, Native North Americans represent a singular opportunity to study genetic contributions to rheumatic disease. For clinicians, the index of suspicion for rheumatic diseases in North American Indians and Eskimos should be high, and the severe disease and sometimes atypical presentations kept in mind.

Digital necrosis as a paraneoplastic syndrome.

We describe a 62-year-old woman who developed sudden onset of digital ulceration and necrosis with high titres of antinuclear antibodies and cutaneous vasculitis who was found to have small cell lung cancer. The combination of antinuclear antibodies, vasculitis, and digital ulceration has not been previously described in association with malignancy, although malignancy has been reported with each of these findings independently. The literature on digital necrosis as a paraneoplastic syndrome is reviewed and possible mechanisms discussed. This case is typical of the majority of those reported, in that the digital necrosis preceded the diagnosis of the malignancy, only the upper extremities were involved, the underlying malignancy was a carcinoma, and while treatment directed at the vasculitis was ineffective, there was rapid improvement of the digital lesions with treatment of the lung tumor. The most likely mechanism for these findings is a systemic vasculitis related to undefined tumor antigens. Unexplained digital necrosis should prompt a search for malignancy.