It is well accepted that patients with antibodies against cyclic citrullinated peptides (anti-CCP) and rheumatoid arthritis (RA) suffer from more severe forms of RA in terms of clinical presentation and radiographic destruction at long term compared to anti-CCP-negative patients. The purpose of this cross-sectional study was to investigate whether the measures of self-reported health among patients with RA of 0.05). Both groups of RA patients reported significantly more physical disabilities in everyday life and significantly poorer physical health than the controls (both p
To update estimates of cancer risk in SLE relative to the general population.
A multisite international SLE cohort was linked with regional tumor registries. Standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected cancers.
Across 30 centres, 16,409 patients were observed for 121,283 (average 7.4) person-years. In total, 644 cancers occurred. Some cancers, notably hematologic malignancies, were substantially increased (SIR 3.02, 95% confidence interval, CI, 2.48, 3.63), particularly non-Hodgkin's lymphoma, NHL (SIR 4.39, 95% CI 3.46, 5.49) and leukemia. In addition, increased risks of cancer of the vulva (SIR 3.78, 95% CI 1.52, 7.78), lung (SIR 1.30, 95% CI 1.04, 1.60), thyroid (SIR 1.76, 95% CI 1.13, 2.61) and possibly liver (SIR 1.87, 95% CI 0.97, 3.27) were suggested. However, a decreased risk was estimated for breast (SIR 0.73, 95% CI 0.61-0.88), endometrial (SIR 0.44, 95% CI 0.23-0.77), and possibly ovarian cancers (0.64, 95% CI 0.34-1.10). The variability of comparative rates across different cancers meant that only a small increased risk was estimated across all cancers (SIR 1.14, 95% CI 1.05, 1.23).
These data estimate only a small increased risk in SLE (versus the general population) for cancer over-all. However, there is clearly an increased risk of NHL, and cancers of the vulva, lung, thyroid, and possibly liver. It remains unclear to what extent the association with NHL is mediated by innate versus exogenous factors. Similarly, the etiology of the decreased breast, endometrial, and possibly ovarian cancer risk is uncertain, though investigations are ongoing.
Studies have raised concern on the cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs). We studied safety of NSAID therapy in a nationwide cohort of healthy individuals.
With the use of individual-level linkage of nationwide administrative registers, we identified a cohort of individuals without hospitalizations 5 years before first prescription claim of NSAIDs and without claimed drug prescriptions for selected concomitant medication 2 years previously. The risk of cardiovascular death, a composite of coronary death or nonfatal myocardial infarction, and fatal or nonfatal stroke associated with the use of NSAIDs was estimated by case-crossover and Cox proportional hazard analyses. The entire Danish population age 10 years or more consisted of 4,614,807 individuals on January 1, 1997, of which 2,663,706 (57.8%) claimed at least 1 prescription for NSAIDs during 1997 to 2005. Of these; 1,028,437 individuals were included in the study after applying selection criteria regarding comorbidity and concomitant pharmacotherapy. Use of the nonselective NSAID diclofenac and the selective cyclooxygenase-2 inhibitor rofecoxib was associated with an increased risk of cardiovascular death (odds ratio, 1.91; 95% confidence interval, 1.62 to 2.42; and odds ratio, 1.66; 95% confidence interval, 1.06 to 2.59, respectively), with a dose-dependent increase in risk. There was a trend for increased risk of fatal or nonfatal stroke associated with ibuprofen treatment (odds ratio, 1.29; 95% confidence interval, 1.02 to 1.63), but naproxen was not associated with increased cardiovascular risk (odds ratio for cardiovascular death, 0.84; 95% confidence interval, 0.50 to 1.42).
Individual NSAIDs have different degrees of cardiovascular safety, which must be considered when choosing appropriate treatment. In particular, rofecoxib and diclofenac were associated with increased cardiovascular mortality and morbidity and should be used with caution in most individuals, whereas our results suggest that naproxen has a safer cardiovascular risk-profile.
To evaluate the possible biological role of pregnancy on the risk of autoimmune diseases we assessed associations between reproductive history and subsequent risk of autoimmune diseases characterized by female predominance and other autoimmune diseases. Our study cohort comprised 4.6 million Danes born since 1935 for whom a complete record of childbirths was available. Cohort members were followed for hospital contacts for 31 autoimmune diseases from 1982 to 2008. Female predominant autoimmune diseases were those with a female:male sex ratio >2:1. Ratios of first hospitalization rates were calculated using Poisson regression, adjusting for potential confounding by age, birth cohort, calendar period and marital status. During 45.5 million person-years of follow-up 102,260 women were hospitalized with one or more autoimmune diseases. Overall, compared with childless women, women with children were at a relative risk of 1.04 (1.02-1.06) for any autoimmune diseases, 1.11 (1.08-1.14) for female predominant and 0.97 (0.95-1.00) for other autoimmune diseases. Possibly biologically related associations with parity were found for Hashimoto thyroiditis (1.11; 1.00-1.24), Graves' disease (1.19; 1.14-1.24), erythema nodosum (1.15; 1.01-1.32), psoriasis (1.08; 1.01-1.15), sarcoidosis (1.17; 1.06-1.28) and systemic lupus erythematosus (0.83; 0.74-0.93). Especially the one-year postpartum period was associated with an increased risk of Hashimoto thyroiditis, Graves' disease and sarcoidosis. Overall, parity was associated with an 11% increased risk of female predominant autoimmune diseases. Pregnancies resulting in liveborn children therefore seem to contribute only little to the general female predominance in autoimmune diseases. However, for a number of autoimmune diseases; especially autoimmune thyroid diseases, erythema nodosum and sarcoidosis parity might somehow be involved in disease development.
To determine the concordance of systemic lupus erythematosus (SLE) and co-aggregating autoimmune diseases among Danish twins.
SLE-affected twins were ascertained by record linkage between the National Patient Register (NPR) and the Danish Twin Registry (DTR). Registered SLE codes were validated through medical chart review and information from the treating physicians. Twin pairs with at least one chart-validated SLE proband were invited to participate in a personal interview and clinical validation of the SLE diagnoses.
Twenty-two twins fulfilled the ACR criteria for SLE. The age- and sex-adjusted point SLE prevalence in the Danish twin cohort was 30.3 per 100,000 persons (95% CI: 19.2-46.5). Among seven monozygotic (MZ), eight same-sex dizygotic (DZss) and five opposite-sex dizygotic (DZos) twin pairs, one MZ and one DZss were concordant for SLE. This corresponded to probandwise concordance rates of 25.0% (95% CI: 7.15-59.1) and 7.7% (95% CI: 1.37-33.3), and pairwise concordance rates of 14.3% (95% CI: 2.57-51.3) and 7.7% (95% CI: 1.37-33.3) among MZ and DZ twins, respectively. An SLE diagnosis was clinically validated in 17 twins from 15 twin pairs. Another four co-twins had other autoimmune disease, corresponding to a probandwise concordance of any autoimmune disease of 50.0% in MZ (95% CI: 21.5-78.5) and 23.1% in DZ twins (95% CI: 8.18-50.3).
Population-based Danish data suggest that SLE twin concordance is lower than previously reported, but still point to the importance of both genetic and environmental factors, and indicate a substantial co-aggregation of other autoimmune diseases in SLE twins.
BACKGROUND: Patients with rheumatoid arthritis (RA) have increased risk of atherosclerosis and cardiovascular disease (CVD) that cannot be explained by excess of traditional risk factors. Several studies indicate that mannose-binding lectin (MBL) may modify the development of atherosclerosis; both high and low serum levels of MBL are reported to be associated with CVD. Intima-media thickness of the common carotid artery (ccIMT) is a validated non-invasive anatomic measure of subclinical CVD. We examined the relation between ccIMT and MBL in 114 RA patients. METHODS: In a cross-sectional study MBL2 genotypes and serum concentrations of MBL were assessed; ccIMT was determined by means of ultrasonography; traditional and RA related cardiovascular risk modifiers were measured. RESULTS: The median ccIMT was 0.67 mm. The investigated MBL2 genotypes were not significantly associated with ccIMT. Using a general linear model, ccIMT was not linearly associated with serum MBL but was highly associated with the quadratic term of serum MBL (MBL(2)) (P=0.001) reflecting a U-shaped relation. MBL(2) was also significantly associated with ccIMT in a multivariable analysis adjusting for traditional and RA related cardiovascular risk modifiers (P=0.025). CONCLUSION: In RA patients, a quadratic U-shaped relation between serum MBL and ccIMT was observed independently of the effects of traditional and RA related risk factors for CVD. These results provide further support to the notion that both high and low levels of MBL may be associated with CVD.
STUDY DESIGN: A randomized controlled comparative trial with an 8-month follow-up period was conducted. OBJECTIVE: To compare the effect of the McKenzie treatment method with that of intensive dynamic strengthening training in patients with subacute or chronic low back pain. SUMMARY OF BACKGROUND DATA: Randomized studies indicate that the efficacy of the McKenzie method in the treatment of patients with acute or subacute low back pain is debatable. Currently, no randomized studies examining the effects of this method for patients with chronic low back pain have been published. METHODS: For this study, 260 consecutive patients with low back pain and at least 8 weeks duration of symptoms (85% of the patients had more than 3 months duration of symptoms) were randomized into two groups: Group A was treated with the McKenzie method (n = 132), and Group B was treated with intensive dynamic strengthening training (n = 128). The treatment period for both groups was 8 weeks at an outpatient clinic, followed by 2 months of self-training at home. Treatment results were recorded at the end of the treatment period at the clinic, then 2 and 8 months after. In both groups, 30% of the patients were lost to follow-up evaluation. An intention-to-treat analysis of the main effect variables, disability, and pain was performed for all the patients included in the study. A supplementary analysis of the 180 patients who completed the full treatment program also was undertaken. RESULTS: Intention-to-treat analysis showed a tendency toward a difference in reduction of disability in favor of the McKenzie group at the 2-month follow-up assessment (P = 0.04), but no differences at the end of treatment and at the 8-month follow-up evaluation. No differences in reduction of pain were observed at any time between the groups. The supplementary analysis of the patients who had completed the full intervention showed a tendency toward a difference in favor of the McKenzie method in reduction of pain at the end of treatment (P = 0.02). This difference reached statistical significance at the 2-month follow-up assessment (P = 0.01), but no difference was found after 8 months. The supplementary analysis showed no differences between the groups with regard to reduction of disability. CONCLUSION: The McKenzie method and intensive dynamic strengthening training seem to be equally effective in the treatment of patients with subacute or chronic low back pain.
Comment In: Spine. 2002 Aug 15;27(16):170912195059
To provide population-based estimates of relative risk of SLE and other autoimmune diseases (ADs) in relatives of SLE patients.
A cohort of 5 237 319 Danish residents identified through the Civil Registration System was coupled to their relatives through the parental link and followed for SLE and other ADs between 1977 and 2013 through linkage to the National Patient Register. Twin zygosity was established through the Danish Twin Registry. Hazard ratios (HRs) with 95% CIs were calculated using Cox proportional hazards regression analyses.
During 117.5 million person-years of follow-up, 3612 persons were hospitalized with SLE. HRs of SLE were high among first-degree (HR = 10.3; 95% CI: 8.25, 12.9; n = 80) and second- or third-degree relatives of SLE patients (HR = 3.60; 95% CI: 2.20, 5.90; n = 16). HRs for any AD were elevated in first-degree (HR = 1.51; 95% CI: 1.41, 1.62; n = 785) and second- or third-degree relatives of SLE patients (HR = 1.28; 95% CI: 1.18, 1.39; n = 582). Among individuals with SLE-affected first-degree relatives, the risk was significantly increased for RA (HR = 1.64; 95% CI: 1.35, 1.99; n = 103), IBD (HR = 1.21; 95% CI: 1.02, 1.43; n = 130) and type 1 diabetes mellitus (HR = 1.23; 95% CI: 1.01, 1.48; n = 106). Risk of other ADs was significantly increased both among SLE-affected first-degree (HR = 2.08; 95% CI: 1.88, 2.31; n = 371) and second- or third-degree relatives (HR = 1.38; 95% CI: 1.23, 1.54; n = 313).
Family history of SLE is associated with a clearly elevated risk of SLE and, to a much lesser degree, of RA and other ADs.
Patients with systemic lupus erythematosus (SLE) have excess cardiovascular morbidity and mortality due to accelerated atherosclerosis that cannot be attributed to traditional cardiovascular risk factors alone. Variant alleles of the mannose-binding lectin gene (MBL2) causing low serum concentrations of functional mannose-binding lectin (MBL) are associated with SLE and development of atherosclerosis. Recent studies show that these variant alleles are associated with increased risk of arterial thrombosis and cardiovascular disease in patients with SLE. Intima-media thickness of the common carotid artery (ccIMT) is a validated noninvasive anatomic measure of subclinical atherosclerosis. In a cross-sectional study we examined the relation among ccIMT, MBL2 genotypes, and serum concentrations of MBL.
The MBL2 extended genotypes (YA/YA, YA/XA, XA/XA, YA/YO, XA/YO, YO/YO) and serum concentrations of MBL were determined in 41 outpatients with SLE. ccIMT was measured by means of ultrasonography. Traditional and nontraditional cardiovascular risk modifiers were assessed and controlled for.
Using nonparametric Mann-Whitney tests we found a significant difference in ccIMT between low-expressing (XA/XA+YA/YO+XA/YO+YO/YO) and high-expressing (YA/YA+YA/XA) MBL2 genotypes (p = 0.034). The difference in ccIMT remained significant in multivariable analysis adjusting for traditional and nontraditional cardiovascular risk modifiers (p = 0.049). ccIMT was negatively correlated to serum concentrations of MBL (Spearman rho = -0.33, p = 0.037). This relation also remained significant in multivariable analysis (p = 0.042).
In this group of SLE patients, MBL2 low-expressing genotypes and low serum levels of MBL were correlated with ccIMT, independent of the effects of traditional and nontraditional cardiovascular risk modifiers.
Patients with systemic lupus erythematosus (SLE) seem to experience an increased prevalence of oncogenic virus infections. The aim of the present study was to investigate whether SLE patients have an increased risk of virus-associated malignancies, defined as malignancies potentially caused by virus infection.
A hospital-based cohort of 576 SLE patients was linked to the Danish Cancer Registry. The cohort was followed up for malignancies from the date of SLE diagnosis, and standardized incidence ratios (SIRs) were calculated for various forms of cancer.
The median duration of followup was 13.2 years. Compared to the general population, the patients experienced an increased overall risk of cancer (SIR 1.6 [95% confidence interval (95% CI)] 1.2-2.0). We observed an increased risk of virus-associated cancers combined (SIR 2.9 [95% CI 2.0-4.1]). Among human papillomavirus (HPV)-associated malignant and premalignant conditions, high risk was found for anal cancer (SIR 26.9 [95% CI 8.7-83.4]), vaginal/vulvar cancer (SIR 9.1 [95% CI 2.3-36.5]), epithelial dysplasia/carcinoma in situ of the uterine cervix (SIR 1.8 [95% CI 1.2-2.7]), and nonmelanoma skin cancer (SIR 2.0 [95% CI 1.2-3.6]). Increased SIRs were also found for other potentially virus-induced cancer types (liver cancer SIR 9.9 [95% CI 2.5-39.8], bladder cancer SIR 3.6 [95% CI 1.4-9.7], and non-Hodgkin's lymphoma SIR 5.0 [95% CI 1.9-13.3]).
The patients in this SLE cohort experienced an increased risk of HPV-associated tumors and other potentially virus-induced cancers during long-term followup. Our findings call for clinical alertness to oncogenic virus infections in SLE patients.