Lupus

This study Identifies the possible risk factors for osteonecrosis (ON) in a homogenous group of early system lupus erythematosus (SLE). Forty-six consecutive SLE patients (<5 years duration) followed at the Lupus Clinic, were enrolled between 2004 and 2005. An extensive clinical and laboratory evaluation using a standard electronic protocol established since 1999, including osteonecrosis symptoms and appropriate magnetic resonance imaging (MRI), were carried out at 1—6 months intervals. All other asymptomatic for osteonecrosis patients at study entry underwent MRI. ON confirmed by MRI was found in 10 of 46 patients (22%). Age, disease duration, clinical vascular features, frequency of thrombophilia and hypofibrinolysis factors and the lipoprotein profile were comparable in patients with and without osteonecrosis (P > 0.05). Remarkably, the frequency of patients with system lupus erythematosus disease activity index (SLEDAI) ≥8 in the previous year of osteonecrosis clinical diagnosis was significantly higher when compared to patients without this manifestation (60.0% versus 19.4%, P = 0.011), supported by the higher glucocorticoid cumulative dose in the same period (P = 0.045). In contrast, these two parameters evaluated in 13th—24th months preceding osteonecrosis diagnosis were similar in patients with and without osteonecrosis (P > 0.05). In the logistic regression analysis only SLEDAI remained as an independent risk factor for ON (OR = 6.78, CI = 1.05—43.55, P = 0.04). Disease activity in the previous year of ON clinical diagnosis is the main predictor factor for the development of this complication in early SLE. Lupus (2007) 16, 239—244.

Deficiency of mannan-binding lectin (MBL) has been reported to impact susceptibility to severe infections and atherosclerosis in systemic lupus erythematosus (SLE). In this study, MBL gene polymorphisms were analysed in 143 SLE patients and the frequency of severe infections and organ damage according to SLICC/ACR Damage Index regarding cerebrovascular accidents, angina pectoris, coronary by-pass surgery, myocardial infarction and peripheral arterial disease leading to significant tissue loss, were recorded during a mean follow-up time of 15 years from diagnosis. In a multiple logistic regression model, smoking (P = 0.001), hypertension (P = 0.030), alcohol intake (P = 0.027) and higher triglyceride concentration (P = 0.026) were associated with cerebrovascular, cardiovascular and peripheral arterial organ damage (CPAD), while the association with MBL deficiency did not reach significance (P = 0.098). Alcohol intake (>15 g/month) was inversely correlated with CPAD (OR = 0.29, 95%CI 0.096—0.87). MBL deficiency was not significantly more common in SLE patients with severe infections in a multivariate analysis (P > 0.3). In conclusion, classical risk factors such as smoking, hypertension, low alcohol intake and elevated triglyceride concentration were relatively more important for development of CPAD than MBL deficiency in SLE. Furthermore, MBL deficiency did not contribute to development of major infections in SLE. Lupus (2007) 16, 245—253.

To determine the clinical relevance of `scleroderma-pattern' (SD-pattern) in mixed connective tissue disease (MCTD), 63 (MCTD) patients (Kasukawa's criteria) were consecutively selected. The main inclusion criterion was availability of previous nailfold capillaroscopy (NC) five years before inclusion. At entry, organ involvement and autoantibody evaluation were performed. The mean age and disease duration were 45.3 ± 10 and 8.45 ± 5.42 years, respectively. SD-pattern was observed in 41 patients at entry (65%) and in 45 at previous NC (71.5%), P = 0.20. Ten patients (16%) changed NC, seven normalized, and three developed SD-pattern. Disease duration, number and frequency of organ involvement were similar in patients with and without SD-pattern. In contrast, analysis of each SD-pattern parameter revealed a significantly lower frequency of moderate/severe avascular areas (AA) at entry compared to previous examination (26.5 versus 53%, P = 0.013). Moreover, 76% of patients with interstitial lung disease (HRCT) had AA at entry, whereas only 24% of patients with this alteration did not have this NC finding (P = 0.017). Furthermore, reduced capillary density was more frequently observed in patients taking immunosuppressive therapy than in those without this medication (66.7 versus 33.3%, P = 0.001). NC in MCTD is a dynamic process and analysis of each SD-pattern parameter seems to be a good indicator of lung involvement and disease severity. Lupus (2007) 16, 254—258.

Antiphospholipid and anti-oxidized LDL (anti-oxLDL) antibodies are associated with thrombosis and atherosclerosis. Rheumatoid arthritis (RA) is characterized by excess atherosclerosis and cardiovascular diseases. Our aim was to determine whether antiphospholipid and anti-oxLDL antibodies are associated with early atherosclerotic changes in RA. The levels of IgG and IgM anticardiolipin, IgG and IgM anti-beta-2-glycoprotein-I and anti-oxLDL autoantibodies have been evaluated in 82 patients having RA. Carotid artery intima-media thickness (IMT) was measured in the carotid arteries in the common carotid, bifurcation and internal carotid arteries. Elevated levels of IgG anticardiolipin antibodies were detected in 17 of 82 (21%) RA patients, including 7 with medium-to-high levels considered being clinically relevant. These patients had significantly elevated mean carotid and carotid bifurcation IMT compared with RA patients without elevated anticardiolipin. No such association was found regarding other autoantibodies tested. Anticardiolipin antibodies are prevalent in RA and are associated with early atherosclerotic changes, supporting a rational for measuring them in RA, and upon detection treat the patients in order to decrease chances of atherosclerosis progression and thrombosis. Lupus (2007) 16, 259—264.

We investigated whether premature telomeric loss occurred in peripheral polymorphonuclear neutrophils (PMN) as well as mononuclear cells (MNC) from patients with systemic lupus erythematosus (SLE). We measured the telomere length of MNC and PMN in 60 SLE patients and 26 sex-, race- and age-matched healthy volunteers by Southern blotting with chemiluminescence method. The possible predisposing factors associated with telomere change were also analysed. We found the telomere length of MNC and PMN shortened with age in different degrees in both SLE and control groups. Compared to the control group, the telomere length was shortened in both SLE-MNC (6.08 kb in SLE versus 6.71 kb in control, P = 0.0008) and PMN (6.24 kb in SLE versus 6.75 kb in control, P = 0.0025). The average reduction in telomere length in SLE patients was equivalent to a premature senescence of 16.5 years in MNC and 13.4 years in PMN. In addition, the accelerated telomere shortening was more prominent in SLE patients younger than 45 years old. SLE disease activity (SLEDAI) contributed remarkably to the accelerated telomere erosion, at least in PMN. Moreover, the telomere length of MNC was significantly shorter than PMN in the same SLE patients with leukopenia and lymphopenia. These data suggested that MNC and PMN from patients with SLE displayed premature and accelerated telomere shortening that SLE is an independent factor for it. Lupus (2007) 16, 265—272.

Low-density lipoprotein (LDL) pathway in systemic lupus erythematosus (SLE) patients taking chloroquine diphosphate (CDP) was evaluated through the kinetic behavior of a radioactive cholesterol-rich nanoemulsion (LDE) that resembles the LDL lipidic structure. LDE was labeled with ¹⁴C-cholesteryl ester (¹⁴C-CE), then IV injected in inactive female SLE patients: 10 taking CDP (CDP), 10 without therapy (NO THERAPY); and 10 normal subjects (CONTROL). Groups were age-matched and followed rigorous selection criteria of conditions that interfere in the lipid profile. Blood samples were collected in pre-established intervals after infusion for radioactivity measurement. Fasting lipoproteins were determined in the beginning of kinetic studies. Fractional clearance rate (FCR) of ¹⁴C-CE was significantly different in the three groups (P = 0.03). In fact, a greater FCR of ¹⁴C-CE was observed in CDP compared to NO THERAPY (0.076 ± 0.037 versus 0.046 ± 0.021 h^{— 1}; P < 0.05) and to CONTROL (0.0516 ± 0.0125 h^{— 1}; P < 0.05). Accordingly, a significant lower total and LDL cholesterol were observed in CDP (156 ± 16 and 88 ± 16 mg/dl) compared to NO THERAPY (174 ± 15 and 108 ± 17 mg/dl; P < 0.05) and to CONTROL (200 ± 24 and 118 ± 23 mg/dl; P < 0.05). In contrast, no difference in (FCR) of ¹⁴C-CE of NO THERAPY and CONTROL groups was observed. This is the first in vivo demonstration that LDE removal by LDL receptor from plasma is increased in SLE patients taking CDP with a consequent beneficial decrease in LDL-c levels. Lupus (2007) 16, 273—278.

Pulmonary arterial hypertension (PAH) in patients with systemic lupus erythematosus (SLE) is uncommon but is associated with poor survival. This study aimed to examine the long-term effects of bosentan, a dual endothelin-1 receptor antagonist, on symptomatology, haemodynamics and quality of life measures in SLE patients with symptomatic PAH. Four local patients had been followed up prospectively with pre-defined protocol during 12-months of bosentan treatment. Six minute walk distance (6MWD), NYHA functional class, Borg Dyspnoea Index (BDI) and SF-36 were measured at 0, 3, 6, 9 and 12 months. Systolic pulmonary arterial pressure (PAP) was measured by transthoracic echocardiography at zero, six and 12 months. Clinical parameters were analysed, pooling data from other SLE patients reported in the literature (n = 4). Bosentan was found to result in significant improvement in 6MWD compared to baseline [+24.8 m, +26.2 m, +54 m and +62.7 m at three (P = 0.001), six (P = 0.001), nine (P = 0.24) and 12 (P = 0.01) months respectively]. A differential effect was found with greater response in patients with lower exercise capacity. This was accompanied by decrease in NYHA functional class, BDI, transient or sustained drop in systolic PAP and mild improvement in SF-36 domains including mental health, vitality, social function and general health. Significantly deranged liver function was found in one patient. Lupus (2007) 16, 279—285.

We present a young woman who was diagnosed as primary antiphospholipid syndrome (deep vein thrombosis and pulmonary embolism in 1999; moderate thrombocytopenia with high-positive anticardiolipin ELISA tests in 2002, and cerebral thrombosis in 2003), and then developed hairy cell leukemia (massive splenomegaly, neutropenia, hairy cells in blood smear and bone marrow trephine biopsy in 2004). A partial remission was achieved with interferon-alpha 2a therapy. After the initiation of 2-chloro-deoxyadenosine therapy, splenomegaly disappeared, the percentage of hairy cells on the bone marrow reduced below 1%, platelet count returned to normal levels. After complete remission was achieved for hairy cell leukemia proved by bone marrow trephine biopsy, antiphospholipid antibodies were found to be negative, and no further thromboembolic complications and thrombocytopenia were seen. In our literature search, we found only six cases that had both antiphospholipid antibodies and hairy cell leukemia. Our case is the first case of antiphospholipid syndrome before the development of hairy cell leukemia. Both hairy cell leukemia and antiphospholipid syndrome responded to lymphocytotoxic treatment with 2-chloro-deoxyadenosine. Lupus (2007) 16, 286—288.

The present study aims to report a-20-year old girl with systemic lupus erythematosus (SLE) who developed myocardial infarction (MI) and also aims to review acute myocardial infarction (AMI) in young SLE cases (≤35 years) reported in the literature. We conducted a comprehensive review of the English literature from 1975 to 2006 to analyse data on MI in SLE patients who had developed AMI either at 35 or earlier. In 32 English articles, we identified 49 SLE patients, plus our case, with AMI. They consist of 41 female and nine male patients, their mean age being 24 ± 6.4 years (range of 5—35). Disease duration varied between 0 and 13 years. The lag time between the onset of the SLE manifestations and development of AMI was 7.7 ± 5.4 year (range of 1 month to 20.5 years). We divided the patients into three subgroups according to their coronary involvement type (Group I: normal coronary artery or coronary thrombosis (n = 16); Group II: coronary aneurysm/arteritis (n = 12); Group III: coronary atherosclerosis (n = 22)). The lag time between the onset of the SLE manifestations and development of MI in the subgroups showed variations: Group I < Group II < Group III. Both prevalence of renal involvement and steroid therapy were higher in patients with coronary atherosclerosis than were in Group I. There were one or more risk factors for atherosclerosis in 39 SLE patients. AMI in young SLE patients may be seen, albeit rare. We suggest that clinicians should have a low threshold for cardiac evaluation in patients with SLE. Also, traditional risk factors could be managed through preventive measures. Lupus (2007) 16, 289—297.

The objective of this study was to analyse whether patients with systemic lupus erythematosus (SLE) without traditional risk factors for coronary artery disease (CAD) develop subclinical myocardial ischaemia in the first years after diagnosis. A cross-sectional analysis of a cohort of 200 female SLE patients was conducted. We selected those patients who fulfilled the American College of Rheumatology (ACR) SLE criteria and had no traditional risk factors for CAD, including diabetes mellitus, hypertension, obesity, hyperlipidemia, and smoking. After an initial clinical and laboratory examination, patients were evaluated using a baseline echocardiogram and a dobutamine and atropine stress echocardiogram to search for subclinical myocardial ischaemia. Forty-one patients were included in the study. The mean age at the time of the study was 34.5 ± 9.56 years (mean ± SD). The mean age at diagnosis was 30.3 ± 9.39 years. The mean time from diagnosis was 3.9 ± 3.3 years. Baseline disease activity index (MEX-SLEDAI score) showed that 92.6% of patients had disease activity, although most patients had mild activity. A dobutamine and atropine stress echocardiogram was performed in 40 patients. All 40 patients had negative tests for subclinical myocardial ischaemia. Patients without traditional risk factors for CAD do not have an increased risk for subclinical myocardial ischaemia in the first years after diagnosis. A longitudinal follow-up study of these patients is needed to confirm our findings and assess if additional non-traditional risk factors for CAD increase the risk for myocardial ischaemia. Lupus (2007) 16, 298—301.