Lupus current issue

Ammonium sulphate precipitation to measure antibodies to double-stranded DNA: a simple clinical test for diagnosis and management of patients with systemic lupus erythematosus

Pincus, T. — Tue, 24 Nov 2009 08:56:19 PST

Polymorphisms in the DNA repair gene XRCC1 and associations with systemic lupus erythematosus risk in the Taiwanese Han Chinese population

Tue, 24 Nov 2009 08:56:19 PST

XRCC1 plays a central role in mammalian DNA repair processes. Two polymorphisms of XRCC1, rs1799782 (Arg > Trp at codon 194) and rs25487 (Arg > Gln at codon 399), are common in the Han Chinese population. Our objective was to analyze the relationship between these two functional single-nucleotide polymorphisms (SNPs) and systemic lupus erythematosus (SLE) in the Taiwanese Han Chinese population. Genotyping was performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) on 172 SLE patients and 160 normal controls. Our data indicate that the frequency of A/G at codon 399 differed between patients and controls (p = 0.01; odds ratio: 1.80; 95% confidence interval: 1.17—2.75), but the allelic frequency analysis did not reveal significant differences. For the SNP at codon 194, there were no differences in either allelic or genotype frequencies between SLE patients and normal subjects. Clinical association studies of SLE symptoms revealed the involvement of the A/G polymorphism at codon 399 in SLE pathogenesis. Our results indicate that a functional SNP at codon 399 of XRCC1 is associated with the development of SLE. Lupus (2009) 18, 1246—1251.

Prognostic factors in patients with systemic lupus erythematosus admitted to the intensive care unit

Tue, 24 Nov 2009 08:56:19 PST

The objectives of this study were to identify risk factors associated with mortality in patients with systemic lupus erythematosus (SLE) admitted to the intensive care unit (ICU) and to evaluate the usefulness of Acute Physiologic and Chronic Health Evaluation (APACHE) II score to predict outcomes in these patients, through the use of a retrospective patient record review from a multidisciplinary intensive care unit in a teaching hospital. One hundred and four patients with SLE admitted to the ICU were included in the study. The mean age of patients was 32.44 years, 96.2% were female and 61.5% were admitted with infection. The mean APACHE II score was 19.7, 46.2% had acute renal dysfunction, 67.3% received inotropics/ vasopressors, 27.9% pulmonary artery catheter and 74% invasive mechanical ventilation. The mean length of stay in ICU was 18.5 days and mortality rate was 32.7%. In the univariate logistic regression analysis, factors associated with mortality were high APACHE II score, use of inotropics/vasopressors, pulmonary artery catheter and invasive mechanical ventilation. High APACHE II score and use of inotropics/vasopressors remained significant in the multi-variate analysis. The area under the receiver operating characteristic curve of the APACHE II score to predict mortality was 0.689 (95% CI 0.586—0.791 p = 0.002) and the Hosmer— Lemeshow ² was 5.094 (p = 0.747). We conclude that the mortality rate in patients with SLE admitted to the ICU is high. The most common cause of admission was infection. The factors associated with mortality were high APACHE II score and the use of inotropics/vasopressors. APACHE II score was unable to accurately predict mortality. Lupus (2009) 18, 1252—1258.

Lack of association between HLA-G 14-bp polymorphism and systemic lupus erythematosus in a Han Chinese population

Tue, 24 Nov 2009 08:56:19 PST

HLA-G is a non-classical HLA-class Ib molecule with multiple immunoregulatory properties. A 14-bp insertion/deletion polymorphism in the HLA-G gene has been suggested to influence the expression of HLA-G and to associate with certain pathological conditions, including autoimmune diseases. We investigated the influence of the 14-bp insertion/deletion polymorphism in the HLA-G gene on disease susceptibility in systemic lupus erythematosus by genotyping this polymorphism in 231 patients with systemic lupus erythematosus and 367 healthy controls and analyzing the levels of soluble HLA-G in a subset of patients with systemic lupus erythematosus and healthy subjects from a Han Chinese population. No statistically significant differences were observed in the frequencies of the 14-bp insertion/deletion HLA-G alleles or genotypes between controls and patients with systemic lupus erythematosus. However, a significant increased expression of soluble HLA-G was noted in patients with systemic lupus erythematosus (mean value = 230.2 U/ml vs 118.3 U/ml in controls, p = 0.0001). Moreover, patients with high levels of soluble HLA-G presented with higher disease activity and had more neurological involvement. Our results do not support the HLA-G 14-bp insertion/deletion polymorphism as a genetic factor influencing systemic lupus erythematosus susceptibility. It is possible that the expression of soluble HLA-G in systemic lupus erythematosus is enhanced as part of a mechanism to try to restore the tolerance process towards auto-antigens and to counteract inflammation. However, the participation of this molecule in the pathological process of the disease also could not be excluded. Lupus (2009) 18, 1259—1266.

Prognostically distinct clinical patterns of systemic lupus erythematosus identified by cluster analysis

To, C., Mok, C., Tang, S., Ying, S., Wong, R., Lau, C. — Tue, 24 Nov 2009 08:56:19 PST

The objective of this study was to evaluate the patterns of clinical manifestations and their mortality in a large cohort of Chinese patients with systemic lupus erythematosus. The cumulative clinical manifestations of a large group of Chinese systemic lupus erythematosus patients who fulfilled at least four American College of Rheumatology criteria for systemic lupus erythematosus were studied. Patients were divided into distinct groups by using the K-mean cluster analysis. Clinical features, prevalence of proliferative lupus nephritis (World Health Organization class III, IV), autoantibody profile, and treatment data were compared and the standardized mortality ratios were calculated for each cluster of patients. There were 1082 patients included in the study (mean age at systemic lupus erythematosus diagnosis 30.5 years; mean systemic lupus erythematosus duration 10.3 years). Three distinct groups of patients were identified. Cluster 1 (n = 347) was characterized predominantly by mucocutaneous manifestations (malar rash, discoid rash, photosensitivity, oral ulcer) and arthritis but having the lowest prevalence of serositis, hematologic manifestations (hemolytic anemia, leukopenia, and thrombocytopenia), and proliferative lupus nephritis. Patients in cluster 2 (n = 409) had mainly renal and hematological manifestations but having the lowest prevalence of mucocutaneous manifestations. Pulmonary and gastrointestinal manifestations were significantly more frequent in cluster 2 than the other clusters. Cluster 3 patients (n = 326) had the most heterogeneous features. Besides having a high prevalence of mucocutaneous manifestations, serositis and hematologic manifestations, renal involvement, and proliferative lupus nephritis was also most prevalent among the three clusters. Patients in cluster 2 had a much higher standardized mortality ratio [standardized mortality ratio 7.23 (6.7—7.7), p < 0.001] than those in cluster 3 [standardized mortality ratio 1.27 (1.1—1.5), p = 0.005] and cluster 1 [standardized mortality ratio 0.95 (0.5—1.7), p = 0.86]. In conclusion, patients with systemic lupus erythematosus could be clustered into prognostically distinct patterns of clinical manifestations. Lupus (2009) 18, 1267—1275.

Sensitivity and specificity of autoantibody tests in the differential diagnosis of lupus nephritis

Tue, 24 Nov 2009 08:56:19 PST

Several studies have investigated the potential of various autoantibody tests in the diagnosis of systemic lupus erythematosus (SLE). Many lupus patients initially present with glomerulonephritis. In that clinical situation the main differential diagnosis are other forms of glomerulonephritis. In this study the diagnostic value of nine test kits for autoantibody against ANA, dsDNA, circulating immune complexes, C1q, nucleosomes, histones and Sm as well as C3 and C4 levels was evaluated in 39 patients with biopsy-proven lupus nephritis in comparison to 43 patients suffering from other forms of glomerulonephritis. The most useful test was an anti-nucleosome antibody enzyme-linked immunosorbent assay (ELISA) with a sensitivity of 90% and a specificity of 88%. All tests for anti-dsDNA antibodies (Crithidia luciliae Anti-dsDNA, BINDAZYME Anti-dsDNA, FARRZYME high avidity Anti-dsDNA) were of moderate sensitivity and very good specificity. Decreasing the cut-off for the conventional anti-dsDNA ELISA (BINDAZYME) considerably increased its sensitivity (87%) without loss of specificity (90%). Tests for anti-C1q and immune complexes performed worse than the antidsDNA tests. As anti-histone and Sm antibodies are present only in a minority of lupus nephritis patients they are of limited value in diagnosing the disease. In conclusion, testing for anti-nucleosome antibodies and the conventional anti-dsDNA ELISA with lower cut-off provide the best diagnostic aids for differentiation of lupus nephritis from other forms of glomerulonephritis. Lupus (2009) 18, 1276—1280.

Work disability in systemic lupus erythematosus is prevalent and associated with socio-demographic and disease related factors

Tue, 24 Nov 2009 08:56:19 PST

Our objectives were to examine the prevalence of work disability (WD) and factors associated with job loss in systemic lupus erythematosus (SLE) in a large, multi-centered Canadian sample to determine the current prevalence of WD and identify the contribution of disease activity, damage, and co-morbidities with respect to WD in this cohort. Cross-sectional data on WD status from the 1000 Canadian Faces of Lupus database (a multi-center multi-ethnic cohort of SLE patients) along with clinical measures (number of ACR criteria ever, SLICC Damage Index, SLAM, SLEDAI, SF-36 and Charlson Co-morbidity Index scores), demographic features (age, sex, high school education, household income, marital status, disease duration, employment status) and co-morbidities (including self-reported fibromyalgia, arthralgias, depression and fatigue) were used in bivariate and logistic regression analyses. The 1137 SLE patients had a mean age of 50 years (SE 0.75) and mean disease duration was 18 years (SE 0.70); 19.09% were work disabled and 49.78% were employed. Those with WD were more likely than non-WD SLE patients to have: a higher number of ACR criteria for SLE; not completed high school; older age; single marital status; a lower household income; longer disease duration; higher SLICC Damage Index and SLAM scores; lower SF-36 PCS and SF-36 MCS scores; less vigorous activity per week; and fibromyalgia, arthralgias, fatigue and depression (p < 0.05). This contemporary rate of WD is lower than many past reports. Socio-demographic factors, co-morbidities (fibromyalgia and fatigue) and disease related factors were strongly associated with WD. We cannot determine cause and effect as the study was cross-sectional. Lupus (2009) 18, 1281—1288.

The relationship between race, cigarette smoking and carotid intimal medial thickness in systemic lupus erythematosus

Scalzi, L., Bhatt, S., Gilkeson, R., Shaffer, M. — Tue, 24 Nov 2009 08:56:19 PST

Racial differences are known to account for a higher incidence of systemic lupus erythematosus (SLE), as well as increased disease severity and mortality. The purpose of this study was to determine whether there are any race-specific risk factors that affect measures of subclinical atherosclerosis in SLE patients. Traditional and SLE-related cardiovascular disease (CVD) risk factors were assessed in 106 female SLE patients. Carotid medial intimal medial thickness (mIMT) and coronary artery calcification (CAC) were measured on all subjects. Differences were evaluated between races for all clinical, serologic, and CVD risk factors and the racial interactions with all covariables. Outcomes included mIMT and CAC. There were no significant differences between races with regard to mIMT or CAC. Significant covariables in the final model for mIMT included age, triglycerides, glucose, and race—age and race—smoking interactions. A prediction model with fixed significant covariables demonstrated that Black subjects with a smoking history had a significantly higher mIMT than Blacks who had never smoked, an effect not seen in Whites. There were no differences between having CAC or with the CAC scores between the races. In the final model for CAC, age and SLE disease duration were significant covariables impacting CAC. When controlling for other significant CVD covariables and interactions, Black women, but not White, with SLE with a history of smoking have higher mIMT measurements than those who have never smoked. This is the first report documenting the race-specific effect of smoking on subclinical measures of CVD in SLE. Lupus (2009) 18, 1289—1297.

An analysis of joint replacement in patients with systemic lupus erythematosus

Mourao, A., Amaral, M., Caetano-Lopes, J., Isenberg, D. — Tue, 24 Nov 2009 08:56:19 PST

A small but important group of patients in our lupus cohort has needed total joint replacement (TJR). Arthritis was identified in 94% of our lupus patients. We have determined how many of our patients needed TJR, explored the risk factors for this procedure in patients with SLE and reviewed the outcome for these patients. Records of the cohort of patients with SLE who have attended our lupus clinic at University College of London Hospital/Middlesex from 1978 to 2008 were reviewed and patients who underwent TJR were identified. We recorded demographic data, other major systemic manifestations of SLE, autoantibody profile, previous use of steroids, other major systemic illnesses, smoking and alcohol habits. Nineteen patients with SLE from our cohort of 500 were found to have at least one TJR. Avascular necrosis (AVN) or concomitant rheumatoid arthritis (RA) was present in the majority of these patients. In contrast, age at disease onset, the presence of anti-cardiolipin antibodies, Raynaud’s phenomenon and smoking habits were not found to be contributing factors for the need to replace joints. Four of our 19 patients (21.1%) had complications of the joint replacement: two of them had infections of the replaced joint, one had a large haematoma immediately after the surgery requiring surgical evacuation and the other had a deep vein thrombosis. None of the patients so far has required joint re-replacement. In conclusion, 4% of SLE patients in our cohort have one or more joints replaced, the majority because of AVN or RA. Lupus (2009) 18, 1298—1302.

Peripheral vascular damage in systemic lupus erythematosus: data from LUMINA, a large multi-ethnic U.S. cohort (LXIX)

Burgos, P., Vila, L., Reveille, J., Alarcon, G. — Tue, 24 Nov 2009 08:56:19 PST

To determine the factors associated with peripheral vascular damage in systemic lupus erythematosus patients and its impact on survival from Lupus in Minorities, Nature versus Nurture, a longitudinal US multi-ethnic cohort. Peripheral vascular damage was defined by the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Factors associated with peripheral vascular damage were examined by univariable and multi-variable logistic regression models and its impact on survival by a Cox multi-variable regression. Thirty-four (5.3%) of 637 patients (90% women, mean [SD] age 36.5 [12.6] [16—87] years) developed peripheral vascular damage. Age and the SDI (without peripheral vascular damage) were statistically significant (odds ratio [OR] = 1.05, 95% confidence interval [CI] 1.01—1.08; P = 0.0107 and OR = 1.30, 95% CI 0.09—1.56; P = 0.0043, respectively) in multi-variable analyses. Azathioprine, warfarin and statins were also statistically significant, and glucocorticoid use was borderline statistically significant (OR = 1.03, 95% CI 0.10—1.06; P = 0.0975). In the survival analysis, peripheral vascular damage was independently associated with a diminished survival (hazard ratio = 2.36; 95% CI 1.07—5.19; P = 0.0334). In short, age was independently associated with peripheral vascular damage, but so was the presence of damage in other organs (ocular, neuropsychiatric, renal, cardiovascular, pulmonary, musculoskeletal and integument) and some medications (probably reflecting more severe disease). Peripheral vascular damage also negatively affected survival. Lupus (2009) 18, 1303—1308.

Gigantomastia in a patient with systemic lupus erythematosus successfully treated by reduction mammoplasty

Lanzon, A., Navarra, S. — Tue, 24 Nov 2009 08:56:19 PST

The objective of the study was to describe a Filipino woman with systemic lupus erythematosus (SLE) who developed gigantomastia associated with hyperoestrogenemia and successfully treated by reduction mammoplasty. A 37-year-old Filipino woman with SLE of 5-year duration presented with enlargement of breasts, which became more noticeable and progressive during disease flares requiring increased steroid dose (±40 mg/day). Following control of the last SLE flare, with prednisone effectively tapered to 15 mg/day, she consented to surgical breast reduction. Preoperative physical examination recorded the right and left breast measurement of 61 cm and 54.5 cm from sternal notch to nipple tip, respectively. serum oestrogen assay was elevated. She successfully underwent reduction mammoplasty with free nipple graft, with an uneventful postoperative course. The breast tissue oestrogen and progesterone receptor assays were strongly positive. In the succeeding months, SLE disease remained stable with prednisone tapered to 10 mg daily. This case illustrates a rare occurrence of gigantomastia associated with hyperoestrogenemia in a patient with SLE, successfully treated with reduction mammoplasty. Lupus (2009) 18, 1309—1312.

Ovarian necrotizing vasculitis in a patient with lupus

Tue, 24 Nov 2009 08:56:19 PST

Ovarian vasculitis is a rare complication seen in the reproductive system and has been described in only one patient with lupus and a few patients with other rheumatic conditions (polyarteritis nodosa, giant cell arteritis, scleroderma). Three additional cases following gynecology procedures have also been reported. We report the second case of a patient with systemic lupus erythematosus, who developed ovarian vasculitis. The diagnosis was made at the age of 12 and confirmed by laparoscopy and histopathology in the presence of disease activity. She experienced late menarche at the age of 16, and she experienced a good clinical evolution after disease treatment with regular menstrual cycles and normal levels of sexual hormones. Lupus (2009) 18, 1313—1315.

Limbic encephalitis associated with systemic lupus erythematosus

Tue, 24 Nov 2009 08:56:20 PST

A 34-year-old woman with systemic lupus erythematosus (SLE) presented with general fatigue, seizures and memory loss. Magnetic resonance imaging of the brain showed a high signal area in the mesial temporal lobe bilaterally. Computed tomography scan of the chest and abdomen and ultrasound of pelvis detected no malignancy and tumour marker, antibodies to antineuronal antibodies (anti-Hu, anti-Ta and anti-Ma) and antibodies to voltage-gated potassium channels were all negative. The present case is limbic encephalitis (LE) associated with SLE and the pathogenesis may include autoimmunity shared. Our experience indicates that the immunologic spectrum of LE will expand to include additional immune mechanisms. Lupus (2009) 18, 1316—1319.

A clinical and epidemiological study of lupus erythematosus at a tertiary referral dermatology clinic in Korea

Bae, Y., Yun, S-J., Lee, J-B., Kim, S-J., Won, Y., Lee, S-C. — Tue, 24 Nov 2009 08:56:20 PST

Dermatological examination is critical for the evaluation of lupus erythematosus. However, little is known about the epidemiology and clinical characteristics of the lupus erythematosus patients that visit dermatology clinics with the chief complaint of skin lesions, especially among Asian populations. We performed this study to determine the epidemiology of cutaneous lupus erythematosus for three subtypes: acute cutaneous lupus erythematosus, subacute cutaneous lupus erythematosus, and chronic cutaneous lupus erythematosus, and for lupus erythematosus non-specific skin disease. Also, we sought to determine the relationship between each type of lupus erythematosus, by the skin manifestations and systemic lupus erythematosus. The medical records of lupus erythematosus patients that were diagnosed by their clinical manifestations, skin biopsy results, and laboratory findings from January 1998 through December 2007 were reviewed. A total of 117 patients were diagnosed with lupus erythematosus; 62 cases had chronic cutaneous lupus erythematosus, 11 had subacute cutaneous lupus erythematosus, and 41 had acute cutaneous lupus erythematosus. The remaining three had systemic lupus erythematosus features with lupus erythematosus non-specific skin lesions such as Raynaud phenomenon, livedo reticularis/vasculitis, non-scarring alopecia, and periungual telangiectasia. The acute cutaneous lupus erythematosus subgroup showed extreme female predominance (9.2:1) whereas subacute and chronic cutaneous lupus erythematosus subgroups did not. Patients with chronic cutaneous lupus erythematosus tended to be older than other groups (peak incidence in the fifth decade). Incidence of laboratory abnormalities, including positive connective tissue markers such as antinuclear, double-strand DNA, and Ro/SS-A antibodies, were present in the order acute, subacute, and chronic cutaneous lupus erythematosus. Acute cutaneous lupus erythematosus almost always indicated systemic involvement of lupus erythematosus, whereas chronic cutaneous lupus erythematosus did not predict the development or existence of systemic lupus erythematosus and had a benign clinical course. Careful consideration of lupus erythematosus non-specific skin lesions may help detect systemic lupus erythematosus regardless of the diagnosis of cutaneous lupus erythematosus. Lupus (2009) 18, 1320—1326.

Abnormal expression pattern of histone demethylases in CD4 + T cells of MRL/lpr lupus-like mice

Long, H., Huang, W., Yin, H., Zhao, S., Zhao, M., Lu, Q. — Tue, 24 Nov 2009 08:56:20 PST

Interleukin-6 release from peripheral mononuclear cells is associated to disease activity and treatment response in patients with lupus nephritis

Esposito, P., Balletta, M. M, Procino, A., Postiglione, L., Memoli, B. — Tue, 24 Nov 2009 08:56:20 PST

Protein-losing enteropathy with mesenteric venous thrombosis: a forme fruste of systemic lupus erythematosus

Chen, W.-L., Tsao, Y.-T. — Tue, 24 Nov 2009 08:56:20 PST

Efalizumab for subacute cutaneous lupus: report of two different outcomes

Tue, 24 Nov 2009 08:56:20 PST

Ovarian vasculitis in an adult with fatal systemic lupus erythematosus

Tue, 24 Nov 2009 08:56:20 PST