Patricia Cagnoli

Population-Based Incidence and Prevalence of Systemic Lupus Erythematosus: The Michigan Lupus Epidemiology and Surveillance Program

OBJECTIVE To estimate the incidence and prevalence of systemic lupus erythematosus (SLE) in a sociodemographically diverse southeastern Michigan source population of 2.4 million people. METHODS SLE cases fulfilling the American College of Rheumatology classification criteria (primary case definition) or meeting rheumatologist-judged SLE criteria (secondary definition) and residing in Wayne or Washtenaw Counties during 2002-2004 were included. Case finding was performed from 6 source types, including hospitals and private specialists. Age-standardized rates were computed, and capture-recapture was performed to estimate underascertainment of cases. RESULTS The overall age-adjusted incidence and prevalence (ACR definition) per 100,000 persons were 5.5 (95% confidence interval [95% CI] 5.0-6.1) and 72.8 (95% CI 70.8-74.8). Among females, the incidence was 9.3 per 100,000 persons and the prevalence was 128.7 per 100,000 persons. Only 7 cases were estimated to have been missed by capture-recapture, adjustment for which did not materially affect the rates. SLE prevalence was 2.3-fold higher in black persons than in white persons, and 10-fold higher in females than in males. Among incident cases, the mean ± SD age at diagnosis was 39.3 ± 16.6 years. Black SLE patients had a higher proportion of renal disease and end-stage renal disease (ESRD) (40.5% and 15.3%, respectively) as compared to white SLE patients (18.8% and 4.5%, respectively). Black patients with renal disease were diagnosed as having SLE at younger age than white patients with renal disease (mean ± SD 34.4 ± 14.9 years versus 41.9 ± 21.3 years; P = 0.05). CONCLUSION SLE prevalence was higher than has been described in most other population-based studies and reached 1 in 537 among black female persons. There were substantial racial disparities in the burden of SLE, with black patients experiencing earlier age at diagnosis, >2-fold increases in SLE incidence and prevalence, and increased proportions of renal disease and progression to ESRD as compared to white patients.

Population-Based Incidence and Prevalence of Systemic Lupus Erythematosus

OBJECTIVE To estimate the incidence and prevalence of systemic lupus erythematosus (SLE) in a sociodemographically diverse southeastern Michigan source population of 2.4 million people. METHODS SLE cases fulfilling the American College of Rheumatology classification criteria (primary case definition) or meeting rheumatologist-judged SLE criteria (secondary definition) and residing in Wayne or Washtenaw Counties during 2002-2004 were included. Case finding was performed from 6 source types, including hospitals and private specialists. Age-standardized rates were computed, and capture-recapture was performed to estimate underascertainment of cases. RESULTS The overall age-adjusted incidence and prevalence (ACR definition) per 100,000 persons were 5.5 (95% confidence interval [95% CI] 5.0-6.1) and 72.8 (95% CI 70.8-74.8). Among females, the incidence was 9.3 per 100,000 persons and the prevalence was 128.7 per 100,000 persons. Only 7 cases were estimated to have been missed by capture-recapture, adjustment for which did not materially affect the rates. SLE prevalence was 2.3-fold higher in black persons than in white persons, and 10-fold higher in females than in males. Among incident cases, the mean ± SD age at diagnosis was 39.3 ± 16.6 years. Black SLE patients had a higher proportion of renal disease and end-stage renal disease (ESRD) (40.5% and 15.3%, respectively) as compared to white SLE patients (18.8% and 4.5%, respectively). Black patients with renal disease were diagnosed as having SLE at younger age than white patients with renal disease (mean ± SD 34.4 ± 14.9 years versus 41.9 ± 21.3 years; P = 0.05). CONCLUSION SLE prevalence was higher than has been described in most other population-based studies and reached 1 in 537 among black female persons. There were substantial racial disparities in the burden of SLE, with black patients experiencing earlier age at diagnosis, >2-fold increases in SLE incidence and prevalence, and increased proportions of renal disease and progression to ESRD as compared to white patients.

Treatment of Lupus Nephritis with Abatacept: The Abatacept and Cyclophosphamide Combination Efficacy and Safety Study

To assess the efficacy and safety of a 24‐week course of abatacept in the treatment of active lupus nephritis and to assess the potential of abatacept to induce “clinical tolerance,” defined as sustained clinical quiescence of lupus nephritis after discontinuation of immunosuppressive therapy.

Diminished white matter integrity in patients with systemic lupus erythematosus.

Purpose Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease that can affect the central nervous system. Neuropsychiatric symptoms are found in 25–70% of patients. Using diffusion tensor imaging (DTI) various studies have reported changes in white matter integrity in SLE patients with neuropsychiatric symptoms (NPSLE patients). The purpose of this study was to investigate, if regional changes in white matter integrity can also be detected in SLE patients without neuropsychiatric symptoms (non-NPSLE patients). Methods Applying DTI and tract based spatial statistics (TBSS) we investigated 19 NPSLE patients, 19 non-NPSLE and 18 healthy controls. Groups were matched for age and sex. Image pre-processing was performed using FSL, following the TBSS pipeline (eddy current correction, estimation of fractional anisotropy (FA), normalization, skeletonization of the group mean FA image). A general linear model with threshold-free cluster enhancement was used to assess significant differences between the three groups. Results Statistical analyses revealed several regions of decreased prefrontal white matter integrity (decreased FA) in both groups of SLE patients. The changes found in the non-NPSLE patients (as compared to healthy controls) overlapped with those in the NPSLE patients, but were not as pronounced. Conclusions Our data suggest that changes in regional white matter integrity, in terms of a decrease in FA, are present not only in NPSLE patients, but also in non-NPSLE patients, though to a lesser degree. We also demonstrate that the way statistical maps are corrected for multiple comparisons has a profound influence on whether alterations in white matter integrity in non-NPSLE patients are deemed significant.

Changes in Regional Brain Morphology in Neuropsychiatric Systemic Lupus Erythematosus.

Objective. Neuropsychiatric lupus (NPSLE) is a severe and potentially life-threatening condition, reported to occur in 25%–70% of patients with systemic lupus erythematosus (SLE). Brain imaging, especially magnetic resonance imaging, is frequently used to diagnose or exclude overt cerebral pathologies such as edema, hemorrhage, and central thrombosis. More advanced imaging techniques have been applied to demonstrate subtle changes in regional cerebral blood flow and brain structure. We investigated changes in regional gray-matter (GM) volume in SLE patients without neurological manifestations and NPSLE patients at an acute stage of the disease. Methods. Using high-resolution structural images and voxel-based morphometry (VBM), we investigated regional GM volume in 20 NPSLE patients (within 2 weeks of the acute manifestation), 18 SLE patients without neurologic and/or psychiatric manifestations, and 18 healthy controls. Results. VBM analyses revealed several regions of GM atrophy in various parts of the brain in NPSLE and SLE patients. GM atrophy was seen in both groups in the temporal and parietal lobes and was most pronounced in the posterior thalamus bilaterally. Both groups showed an increase in regional GM volume in the posterior parahippocampal gyrus. Conclusion. Our data suggest that changes in regional brain morphology are present in acute NPSLE, but also in SLE (as compared to controls), which might be indicative of a subclinical neurodegenerative process. Further research is needed to investigate whether specific neuropsychiatric symptoms are related to these changes.

MR Diffusion Tractography to Identify and Characterize Microstructural White Matter Tract Changes in Systemic Lupus Erythematosus Patients

PURPOSE Systemic lupus erythematosus (SLE) is a predominantly female autoimmune disease that can affect the central nervous system. Neuropsychiatric symptoms are found in 25-70% of SLE patients. Using diffusion tensor imaging, various studies have reported changes in white matter integrity in SLE patients with neuropsychiatric symptoms (NPSLE patients). The purpose of this study was to investigate if changes can be detected in the individual white matter tracts in SLE patients regardless if neuropsychiatric symptoms are present or not. MATERIALS AND METHODS Magnetic resonance diffusion tractography in several individual white matter tracts that are involved in language and memory tasks, including tracts to cortical association areas, was applied in 21 patients with NPSLE (mean age: 40.7 ± 12.8 years; range: 22-67 years), 18 patients with non-neurologic systemic lupus erythematosus (non-NPSLE) (mean age: 40.6 ± 12 years; range: 22-67 years), and 20 healthy control (HC) individuals (mean age: 40.64 ± 12.7 years; range: 19-60 years). Additional patients were evaluated; however, because of the inability to complete the scans required, they were excluded from the study. The fractional anisotropy of individual fiber tracts was measured and correlated with cognitive function and lupus disease severity index (Systemic Lupus Erythematosus Disease Activity Index [SLEDAI]) to assess predictability and diagnostic value of these measures for NPSLE. RESULTS Analyses of variance of the tractography data from the analysis of 21 tracts revealed decreased fractional anisotropy in uncinate fasciculus in the NPSLE patients when compared to non-NPSLE lupus patients and HC individuals (P = 0.002). Non-NPSLE patients also demonstrated decreased fractional anisotropy when compared to healthy patients (P = 0.03). Decreased fractional anisotropy was also identified in the corpus callosum and corona radiata in NPSLE patients when compared to HC individuals; however, these tracts did not show a significant difference between NPSLE and non-NPSLE patients. Decreased fractional anisotropy in the uncinate fasciculus correlated with low SLEDAI score (R2 = 0.32). CONCLUSIONS Diffusion tensor tractography corroborates findings of decreased white matter integrity within the anterior corona radiate as well as the corpus callosum as previously described. Specifically, our study identified changes in the uncinate fasciculus in NPSLE and non-NPSLE patients that correlate with clinical changes (SLEDAI scores) and are independent of conventional T2 lesion burden.