Lupus

Systemic lupus erythematosus (SLE) often coexists with other diseases. Diabetes mellitus (DM) is an example and patients with overlap SLE-DM can present with clinical features common to both disorders. In this review, we describe the patients with overlap SLE-DM, focussing on the clinical features common to both diseases that these patients can present, and on the challenges of managing such complications. A detailed review of the patients’ notes (n = 485) was performed. At every outpatient appointment the patients’ urine was tested for glucose, protein and blood. Patients with persistent glycosuria were investigated with fasting blood glucose and a glucose tolerance test to help make the diagnosis of DM. Particular note was made of those patients whose symptoms could be due to SLE, DM or both. Nine patients with DM were identified. Three had type 1 DM, four had type 2 DM and two were considered to have steroid-induced DM. Among these patients, three had renal involvement (two with WHO class IV lupus nephritis); two had peripheral neuropathy (one had a mixed sensory and motor neuropathy, one had a sensory peripheral neuropathy); two patients had retinopathy and cataracts and one had angina. The combination of SLE and DM is uncommon but the predisposition to renal, peripheral neuropathy and retinal disease means that great care must be taken when deciding which clinical feature is due to which disease, because active SLE requires additional immunosuppression whereas DM requires optimization of the metabolic control. Interestingly, although in theory patients with SLE and DM are in double-jeopardy of developing atherosclerosis, to date, only one of our overlap patients has developed angina.

Little is known about qualitative abnormalities of high-density lipoproteins (HDL) in systemic lupus erythematosus (SLE). We studied distribution and composition of HDL subclasses in 30 premenopausal women with uncomplicated SLE, and 18 controls matched for age and sex. Plasma and HDL lipids were determined by colorimetric enzymatic assays, HDL size distribution by native gradient polyacrylamide gel electrophoresis (PAGE) and apolipoproteins in HDL by sodium dodecyl sulphate denaturing PAGE. Compared with controls, SLE patients had significantly lower proportions of HDL_2b (−14.7%) and higher proportions of HDL_3b (+8.8%) and HDL_3c (+23.3%). Cholesteryl ester (−18%) and apolipoprotein AI (−9%) were lower, whereas triglycerides (+32%) and apolipoprotein E (+27%) were higher in SLE HDL (P < 0.05; for all). In the whole population, stepwise regression analysis showed that only insulin concentrations (R² = 0.327) and plasma total apo AI (R² = 0.114) accounted independently to the variance in HDL size. This study shows that HDL distribution and composition are abnormal in non-complicated SLE patients. These HDL abnormalities have been reported to be associated to impaired atheroprotective properties of HDL and prevalence of coronary heart disease. Therefore, they may contribute to the premature atherosclerosis observed in young women with SLE.

Impaired DNA repair efficiency in systemic lupus erythematosus (SLE) patients has been reported in some studies, mainly regarding the repair of oxidative damage, but little is known about repair kinetics towards primarily single-stranded DNA breaks. In the present study, we aimed to investigate: (a) the efficiency of SLE peripheral blood leucocytes in repairing DNA damage induced by ionizing radiation and (b) the association of DNA repair gene (XRCC1 Arg399Gln, XRCC3 Thr241Met and XRCC4 Ile401Thr) polymorphisms in SLE patients, considering the whole group, or stratified sub-groups according to clinical and laboratory features. A total of 163 SLE patients and 125 healthy controls were studied. The kinetics of DNA strand break repair was evaluated by the comet assay, and genotyping for DNA repair genes was performed by PCR-RFLP. Compared with controls, SLE leucocytes exhibited decreased efficiency of DNA repair evaluated at 30 min following irradiation. A significant association with DNA repair gene polymorphisms was not observed for the whole group of SLE patients; however, the XRCC1Arg399Gln polymorphism was associated with the presence of anti-dsDNA antibody. The concomitance of two DNA repair polymorphic sites was associated with the presence of neuropsychiatric manifestations and antiphospholipid antibody syndrome. Taken together, these results indicated that SLE leucocytes repair less efficiently the radiation-induced DNA damage, and DNA repair polymorphic sites may predispose to the development of particular clinical and laboratory features.

Antiphospholipid antibodies (lupus anticoagulant, anti-cardiolipin and anti-β₂-glycoprotein I antibodies, mostly IgG isotype) are strong risk factors for thrombosis. Because a paucity of information on IgA isotype exists in the literature, we retrospectively evaluated the thrombotic significance of IgA antiphospholipid antibodies. We included 472 patients with clinical information on thrombotic events and complete laboratory work-up for antiphospholipid antibodies syndrome. Odds ratios (OR) of various antiphospholipid antibodies for thrombosis were calculated by univariate and multivariate analyses. Lupus anticoagulant alone was detected in 57 (12%) patients, ELISA-based antibodies (IgG, IgM, IgA) against cardiolipin, phosphatidylserine or β₂-glycoprotein-I alone were detected in 131 (28%) patients, whereas 80 (17%) patients had both. Antibody isotype distribution was IgG 32%, IgM 60% and IgA 56%. Univariate analysis showed a statistically significant risk of thrombosis in patients with elevated titres of IgA of any ELISA-based antiphospholipid antibodies (OR 1.77). Stepwise logistic regression (multivariate) analysis identified elevated titres of any ELISA-based IgA antiphospholipid antibodies as an independent risk factor for thrombosis (OR 1.6) in the entire cohort, and in the subgroup of patients without concurrent presence of lupus anticoagulant (OR 1.8). IgA antiphospholipid antibodies appear to be a significant independent risk factor for thrombosis, thereby meriting evaluation in patients with unexpected thrombosis.

Few large, multi-ethnic studies have examined the clinical and serologic differences between familial and sporadic SLE patients. Understanding these similarities and differences is critical for interpreting genetic studies and developing therapeutic strategies. We compiled information on 1915 patients with SLE in a large multi-racial cohort, including general demographics, pedigree structure and the specific American College of Rheumatology (ACR) criteria met. One patient was randomly selected from each multiplex family for analysis, yielding 554 European-Americans (EA), 373 African-Americans (AA), 193 Hispanics (HI) and 237 patients of other of mixed races. When comparing familial and sporadic patients stratified by race, lupus erythematosus (LE) cells and arthritis were increased in white familial cases (P = 5.5 × 10⁻⁶ and P = 0.028, respectively), but no other significant differences between familial and sporadic patients were found. We found that there were profound differences in clinical profiles between races. For example, photosensitivity and malar rash were decreased in AA (P = 1.3 × 10⁻¹³ and 1.4 × 10⁻⁷, respectively), whereas discoid rash was increased in AA (P = 5.5×10⁻⁶). EA had significantly less renal disease (P = 5.4×10⁻¹³), proteinuria (P = 4 × 10⁻¹²) and anti-Sm (P = 1.7 × 10⁻¹²) than AA or HI. We, therefore, conclude that familial and sporadic onset patients may be treated similarly with respect to clinical and genetic studies.

As endothelial dysfunction is one of the earliest signs of atherosclerosis, which is accelerated in systemic lupus erythematosus (SLE), we assessed whether vascular responses of the cutaneous microcirculation are disturbed in SLE patients and influenced by Raynaud’s phenomenon (RP). Laser Doppler fluxmetry (LDF) was used in combination with iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP), an endothelium-dependent and endothelium-independent vasodilator respectively. 42 SLE patients with inactive disease, 12 of whom had RP and 19 age- and sex-matched controls were included. Furthermore, traditional and non-traditional risk factors for cardiovascular disease (CVD) were assessed, and markers of inflammation and endothelial activation were measured. Vascular responses of SLE patients without RP did not differ from controls. However, SLE patients with RP exhibited decreased vasodilatation compared with controls. SLE patients with RP also had longer arrival times of ACh and SNP than controls. Markers of inflammation and von Willebrand factor were increased in SLE patients. Smoking, the presence of SLE and RP were negatively associated with vascular responses in univariate analysis. In multivariate analyses, the only independent variable of vascular responses to ACh and SNP was the presence of RP. Despite signs of endothelial activation, SLE patients with inactive disease do not have altered vascular responses in the microcirculation compared with controls. In SLE patients with RP, cutaneous vascular responses to both ACh and SNP are impaired. Therefore, LDF of the microcirculation seems not to be the appropriate method to distinguish those SLE patients with an increased risk to develop CVD.

The aim of this study was to evaluate the changes in body composition after glucocorticoid treatment in patients with systemic lupus erythematosus (SLE). Consecutive SLE patients were recruited for serial measurements (baseline, months 2 and 6) of bone mineral density (BMD) and body composition [bone mineral content (BMC), fat and lean mass] by dual energy X-ray absorptiometry scan after high-dose oral glucocorticoid therapy. Factors correlated with changes in body composition were evaluated. 29 SLE patients were studied (age 39.7 ± 11.5 years; 83% women with 29% postmenopausal; SLE duration 80.1 ± 80 months). Fourteen patients (48%) were glucocorticoid-naive. The mean maximum daily dosage of prednisolone was 32.9 ± 6.5 mg and the cumulative prednisolone dosage in 6 months was 2.7 ± 0.7 g. At 6 months, a significant drop in BMC of the trunk (−5.0 ± 2.2%; P = 0.04) and whole body (−1.2 ± 0.4%; P = 0.002) compared with baseline was observed, and so was the BMD of the hip (−1.7 ± 0.6%; P = 0.006) and whole body (−0.7 ± 0.3%; P = 0.01). A significant increase in the fat mass of the trunk (+14.5 ± 4.1%; P = 0.001) and limbs (+10.0 ± 3.2%; P = 0.004), but a non-significant drop in lean mass of the trunk (−3.3 ± 1.8%; P = 0.08) and limbs (−0.8 ± 2.4%; P = 0.75) also occurred. The changes in whole body BMC correlated significantly with age (ρ = −0.51; P = 0.02) and changes in total fat mass (ρ = 0.44; P = 0.02) but not with lean mass (ρ = −0.21; P = 0.27), gender, body mass index, smoking, prednisolone dosages or changes in BMD. In SLE patients, high-dose glucocorticoids lead to an early and rapid drop in bone mass, which is more serious in older patients and correlates with an increase in body fat.

The main objective of this study was to evaluate the clinical differences and the pattern and extent of organ damage in late-onset systemic lupus erythematosus (SLE). A nested case–control study was performed from patients with SLE followed in the Rheumatology Unit of the State University of Campinas between 1974 and 2005. Patients who developed SLE after the age of 49 were considered late-onset SLE. SLE patients with age <49 years, matched for sex, ethnicity, disease duration and organ damage at study entry were randomly chosen to compose the control group. Baseline and cumulative clinical manifestations, laboratory data, SLE disease activity index (SLEDAI), Systemic Lupus International Collaborating Clinics/American College of Rheumatology-damage index (SDI) and mortality were compared between groups. At diagnosis and follow-up, late-onset group had lower SLEDAI scores when compared with younger age onset. Clinically, they presented less frequently arthritis (P = 0.0002) and malar rash (P = 0.02) and more frequently Raynaud’s phenomenon (P = 0.002) and arterial hypertension (P = 0.02) when compared with young onset at diagnosis. Late-onset SLE received lower total corticosteroid dose (P < 0.001) and less frequently cyclophosphamide (P = 0.01). During the study period, late-onset SLE had always lower SLEDAI scores (P = 0.001). At study endpoint, late-onset SLE patients had significantly higher SDI scores (P = 0.001) and a higher mortality rate when compared with younger onset group (P < 0.01). In conclusion, late-onset SLE is milder on presentation and during course of disease, but patients have more organ damage and a higher rate of mortality than young onset SLE. Patients with late onset should be followed with close monitoring and early identification of complications is mandatory in this subgroup of patients with SLE.

Progressive multifocal leucoencephalopathy (PML) is a CNS infection of oligodendrocytes by JC virus, which rarely occurs in lupus, and can be mistaken for antiphospholipid antibody syndrome or neuropsychiatric systemic lupus erythematosus (NSLE). This case of PML in a patient with systemic lupus erythematosus on supra-therapeutic doses of methotrexate emphasises that CNS infection is an important diagnostic consideration before empiric treatment with immunosuppresants for NSLE.

Systemic lupus erythematosus (SLE) is often complicated by pericarditis with effusion, which generally responds well to glucocorticoid. We report herein a Japanese patient with SLE who showed a sign of cardiac tamponade and severe chest and back pain because of massive intractable pericardial effusion. Pulse glucocorticoid and pulse cyclophosphamide gained marginal effects. Pericardial effusion accumulated again soon after ultrasound-guided pericardiocentesis and drainage. Pericardial fenestration performed surgically as a last resort, for draining pericardial fluid into the pleural space, was very effective, and only a much smaller amount of fluid was observed in the space thereafter in comparison with the volume before the surgery. Pathological examination of the retrieved pericardium unfolded intense hyperplasia of small vessels and capillaries. Levels of IL-6 and TNF-α in pericardial effusion were extremely higher than those in serum. Pericardial effusion with extensive capillary hyperplasia in SLE would be resistant to medical treatment and require surgical fenestration.

Progressive multifocal leukoencephalopathy (PML) is a rare, deadly demyelinating disease of the central nervous system, which is caused by a reactivation of the DNA polyomavirus JC and occurs in immunosuppressed individuals. So far, only 25 cases have been described in patients with SLE and none survived without antiviral therapy and only two cases in RA. We present four additional cases from a defined area, three in SLE, of which one survived without antiviral therapy, and one case in RA, also surviving after reduction of immunosuppressive treatment. In three of these cases, diagnosis could only be confirmed by stereotactical brain biopsy, including the two surviving cases. Thus, this article illustrates the difficulty in diagnosing progressive multifocal leukoencephalopathy, the need for brain biopsy in many cases, the importance of reduced immunosuppression as early as possible and the severe damage progressive multifocal leukoencephalopathy can cause. Furthermore, progressive multifocal leukoencephalopathy might be much more common in SLE than expected with 1 case in 800 patient-years.

The aim of this study was to investigate whether initial and accrued organ damage measured by Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (SDI) predicts mortality in cohort of Brazilian patients with systemic lupus erythematosus (SLE). One hundred and five outpatients with SLE were enrolled from July 2000 to March 2001; their demographics, disease manifestations, interventions and quantified disease activity (SLEDAI) were obtained. SDI was measured at baseline and at the end of follow-up. Initial and accrued SDI prognostic values for mortality were investigated by multivariate Cox survival analysis and Kaplan-Meyer survival curves. After a median follow-up of 6.3 years, 19 patients died due to disease activity, end-organ failure, cardiovascular events, cancer and infection. Deceased patients had longer disease duration and greater initial and final SDI than survivors had. After adjustment for age, sex and disease duration, both initial and final SDI ≥ 3 points were independent predictors of mortality, with hazard ratios (HRs) of 3.0 (1.1–8.2) and 4.7 (1.6–14.5), respectively. Damage accrual during follow-up was the strongest predictor of death (HR: 5.1, 2.0–13.0). Renal and pulmonary damages were the main predictors of increased mortality risk. In conclusion, baseline and accrued damage increase mortality risk in Brazilian patients with SLE. Measures to prevent damage development and progression are urgent to reduce the mortality of patients with SLE.