The association between antiphospholipid antibodies (aPL) and clinical events is stronger with a positive lupus anticoagulant (LA) test, higher anticardiolipin antibody (aCL) titers, and/or higher anti-β₂-glycoprotein-I antibody (aβ₂GPI) titers. The objective of this study was to determine the clinical characteristics of persistently high-titer (≥80 U) aCL-positive patients compared with those with persistent moderate aCL titers (40–79 U). Second, we analyzed whether high-titer aβ₂GPI test adds predictive information in persistently moderate-to-high titer aCL-positive patients. In this cross-sectional study, the primary analysis compared the clinical and aPL characteristics of 58 patients with at least two moderate-titer aCL results to another 85 patients with at least two high-titer aCL results. In the secondary analysis of patients with at least two aβ₂GPI test results, we compared 29 patients with ‘aCL 40–79 U and aβ₂GPI < 80 U’ profiles with 8 patients with ‘aCL 40–79U and aβ₂GPI ≥ 80 U’, and also compared 27 patients with ‘aCL > 80 U and aβ₂GPI < 80 U’ with 32 patients with ‘aCL > 80 U and aβ₂GPI ≥ 80 U’. Although aPL-related vascular and pregnancy events were similar between the moderate- and high-titer aCL groups, the number of patients with positive LA tests (RR 2.06, CI 1.38–3.08, p < 0.01) and with at least one non-criteria aPL manifestation (RR 1.66, CI 1.20–2.30, p = 0.0005) were significantly higher in the high-titer aCL group. While magnetic resonance imaging (MRI) white matter changes were statistically more common in the high-titer aCL group (RR 2.03, CI 1.04–3.94, p = 0.02), there was a trend towards increased prevalence of livedo reticularis, cardiac valve disease, and cognitive dysfunction occurring in the high-titer aCL group. The secondary analysis showed that MRI white matter changes, cardiac valve disease, and cognitive dysfunction were proportionally more common in the high-titer aβ₂GPI groups, suggesting a linear relationship between non-criteria aPL manifestations and aPL titers. Our results suggest that patients with high aCL titers, compared with those with moderate titers, are more likely to have a positive LA test and a higher prevalence of non-criteria aPL manifestations. Furthermore, high-titer aβ₂GPI positivity may further increase the prevalence of non-criteria aPL manifestations in moderate- or high-titer aCL-positive patients.

Long-term use of unfractioned heparin data has been associated with a 2.2–5% incidence of heparin-induced osteoporotic fracture, but for low-molecular-weight heparin (LMWH) data is scarce and there is lack of clarity of the risks of osteoporosis and osteoporotic fractures. In this paper we review the differential diagnosis of osteoporosis and osteoporotic fractures, and we conduct a systematic review of all related cases from case reports and trials. Two new cases of possible LMWH-induced osteoporosis are also presented and the difficulties in making the diagnosis are highlighted. The authors conclude that, until large clinical trials are designed to investigate pre- and post-treatment bone density and to compare different dosages of LMWH effect on the bone density in different patient groups, no safe conclusions can be made.

We developed a brief, new health-related quality of life measure for children with systemic lupus erythematosus that is valid in English for the United States, called Simple Measure of Impact of Lupus Erythematosus in Youngsters© (SMILEY©). The United States-English language questionnaire may not be applicable to most of the countries in the world and several United States population subgroups, such as Hispanics. In order to measure the impact of morbidity of systemic lupus erythematosus on the lives of children, adolescents, and their parents and assess the outcome of new therapies, it is critical to have a uniform measure of systemic lupus erythematosus-specific health-related quality of life that is valid for different cultures. We report the translation and cultural adaptation process undertaken by our team with the goal of cross-cultural validation of SMILEY© in the following thirteen languages: Danish, Dutch, French (France), German (Germany), Hebrew, Italian, Portuguese (Brazil), Slovene, Spanish (USA and Puerto Rico), Spanish (Spain), Spanish (Argentina), Spanish (Mexico), and Turkish. We employed the following steps: establishing collaborative relationships with institutions across the globe; forward and back translation of SMILEY© text; and cultural adaptation of SMILEY© content. We are in the process of enrolling patients and conducting validation of the translated and adapted versions of SMILEY©.

The objective of this study was to compare oxidative status and homocysteinemia in patients with lupus nephritis (LN) and in controls. Total antioxidant capacity (TAC), reactive oxygen species (ROS), homocysteine and related vitamins were measured in 68 patients with LN and in 50 controls. LN patients had lower TAC (p = 0.05) and higher ROS and homocysteinemia (p = 0.01) than controls. TAC, significantly lower in active than in quiescent LN (p = 0.01), was correlated with albuminemia (p = 0.02), inversely with proteinuria (p = 0.01) and anti-DNA antibodies (p = 0.004). ROS values, higher both in active and in inactive LN, correlated with age (p = 0.02), C-reactive protein (CRP) (p = 0.0005) and inversely with prednisone dosage (p = 0.05). At multivariate analysis, CRP (p = 0.04) and age (p = 0.005) were independent ROS predictors. Homocysteine, higher in active than in quiescent LN (p = 0.016) and in patients with antiphospholipid antibodies (p = 0.05), correlated with serum creatinine (p = 0.00001) and proteinuria (p = 0.015). At multivariate analysis serum creatinine (p = 0.006) and active nephritis (p = 0.003) were independent predictors of hyperhomocysteinemia. Patients with LN showed impaired oxidative status, even without clinical signs of renal activity. ROS production may be counterbalanced by adequate antioxidant capacity in some patients with quiescent LN. The association of hyperhomocysteinemia and antiphospholipid antibodies positivity may increase the risk of cardiovascular and/or thrombotic events in LN patients.

Our objective was to evaluate the relevance of traditional and disease-related cardiovascular risk factors and of bone mineral density for premature coronary artery calcification in young patients with systemic lupus erythematosus. Ninety-four female patients with systemic lupus erythematosus with disease durations >5 years and <45 years were consecutively selected. Cardiovascular risks (diabetes mellitus, arterial hypertension, dyslipoproteinemia, smoking, family history, body mass index, ovarian and renal insufficiency) and systemic lupus erythematosus-related risk factors (disease duration, ACR criteria, modified SLICC/ACR, SLEDAI and treatment) were evaluated. Bone mineral density was assessed by dual X-ray absorptiometry. Coronary artery calcification was determined by computed tomography. Coronary artery calcification was identified in 12 (12.7%) patients and was associated with a higher frequency of patients with cardiovascular risks (p = 0.001), higher number of cardiovascular risks (p = 0.002), age (p = 0.025), disease duration (p = 0.011) and SLICC (p = 0.011). Individual analysis of cardiovascular risks demonstrated that menopause (p = 0.036), dyslipidemia (p = 0.003) and hypertension (p = 0.006) were significantly associated with coronary artery calcification. In addition, coronary artery calcification was associated with a lower whole body bone mineral density (p = 0.013). Multiple logistic regression analysis using cardiovascular risks, age, disease duration, SLICC and whole body bone mineral density revealed that only disease duration (p = 0.038) and whole body bone mineral density (p = 0.021) remained significant for coronary artery calcification. In conclusion, we found that disease duration and decreased bone mineral density are independent predictors for premature coronary calcification in young women with systemic lupus erythematosus, suggesting a common underlying mechanism.

Differentiation between lymphadenopathy in potentially life-threatening systemic lupus erythematosus (SLE) and self-limiting necrotizing lymphadenitis, also called Kikuchi–Fujimoto disease (KFD), is difficult. In the past, co-occurrence of SLE and KFD has been described repeatedly in case reports. Here, we report a case of necrotizing lymphadenitis, describe the clinical and histopathologic features in detail and discuss the current literature. KFD may in fact be a histopathologic characteristic of SLE supporting the hypothesis that KFD is a rare manifestation of SLE. To clarify whether KFD is the same entity as lupus lymphadenitis, more cases with SLE and lymphadenopathy should be examined in detail.

Abstract: The genes of killer cell immunoglobulin-like receptors (KIRs), which are involved in the activation of T cells and natural killer cells, are highly variable. In recent years, the role of KIRs in autoimmune diseases has received increasing attention. The present study was undertaken to determine the association of the polymorphism of KIR genes with the susceptibility to systemic lupus erythematosus (SLE). The polymorphism of KIR genes of 93 patients with SLE together with 123 healthy donors as the control group was determined by polymerase chain reaction with sequence-specific primers. Twenty-seven novel gene combinations were found. Genotypic frequencies of KIR2DL2 (p < 0.001) and KIR2DS1 (p < 0.001) were much higher in patients with SLE than in control subjects. Individuals with two and more than two activating KIR genes were found more frequently in patients than in control subjects (80.7% versus 66.7%, p = 0.022). The results suggest that a genetic disturbance between activating and inhibitory KIR genes may be one of the key factors underlying the pathogenesis of SLE.

β2-glycoprotein I is the best-characterized antigenic target for antiphospholipid autoantibodies. We synthesized a tetrameric conjugate of the domain 1 of β2-glycoprotein I (LJP 993) aimed at developing the conjugate as a Toleragen to suppress antiphospholipid syndrome. The present studies focused on determining the stability, tissue distribution, plasma concentration-time profile and excretion of the LJP 993 in mice. The stability of LJP 993 in mouse plasma was quantitatively evaluated using strong cation-exchange high performance liquid chromatography. ¹²⁵I-labeled LJP 993 was intravenously injected to mice, and levels of ¹²⁵I-labeled LJP 993 in plasma, tissues, urine and feces were determined at known intervals. Incubation of LJP 993 with mouse serum at 37°C for 8 h resulted in a decrease by 34% of LJP 993 concentration. No degradation fragment was observed during the incubation. After a single intravenous administration of ¹²⁵I-LJP 993 (0.5 and 5 mg/kg) to mice, both C_max and area-under-curve values increased in a dose-proportional manner, and blood radioactivity disappeared in a bi-exponential manner with the distribution half-lives equal to 1.7 min, and the elimination half-lives 188 and 281 min, respectively. The ¹²⁵I-LJP 993 was moderately distributed into organs and tissues with the exception that brain level of ¹²⁵I-LJP 993 was negligible. The major sites of ¹²⁵I-LJP 993 uptake were the kidney (at 30 min post dosing), and kidney, lung, liver, heart, spleen, skin, muscle and fat tissues (at 4 h post dosing). Cumulative urinary and fecal radioactivity for 0–48 h post dosing accounted for 44.7% and 4.2% of the administered dose, respectively, with the fast rate of urinal excretion occurring within the first 8 h. In summary, LJP 993 was fairly stable in mouse plasma. After administration to mice, ¹²⁵I-LJP 993 was taken up mainly by kidney and then distributed extensively to tissues except brain. Both C_max and area-under-curve values increased in a dose-proportional manner. It was predominantly excreted in the urine with an elimination half-life longer than 3 h. Kidney is a major route to excrete the tetrameric conjugate.

Mesenchymal stem cells (MSCs) exert suppressive effects in several disease models including lupus prone mice. However, autologous MSC therapy has not been tested in human systemic lupus erythematosus (SLE). We evaluate the safety and efficacy of bone marrow (BM)-derived MSCs in two SLE patients; the suppressor effect of these cells in-vitro and the change in CD4+CD25+FoxP3+ T regulatory (Treg) cells in response to treatment. Two females (JQ and SA) of 19 and 25 years of age, fulfilling the 1997 American College of Rheumatology (ACR) criteria for SLE were infused with autologous BM-derived MSCs. Disease activity indexes and immunological parameters were assessed at baseline, 1, 2, 7 and 14 weeks. Peripheral blood lymphocyte (PBL) subsets and Treg cells were quantitated by flow cytometry, and MSCs tested for in-vitro suppression of activation and proliferation of normal PBLs. No adverse effects or change in disease activity indexes were noted during 14 weeks of follow-up, although circulating Treg cells increased markedly. Patient MSCs effectively suppressed in-vitro PBL function. However, JQ developed overt renal disease 4 months after infusion. MSC infusion was without adverse effects, but did not modify initial disease activity in spite of increasing CD4+CD25+FoxP3+ cell counts. One patient subsequently had a renal flare. We speculate that the suppressive effects of MSC-induced Treg cells might be dependent on a more inflammatory milieu, becoming clinically evident in patients with higher degrees of disease activity.

The aim of our study was to determine whether the SLEDAI-2K calculated using a timeframe of 30 days prior to a visit for clinical and laboratory variables was equivalent to the prescribed 10-day period. One hundred forty nine consecutive lupus patients seen over 9 weeks at the University of Toronto Lupus Clinic enrolled. The SLEDAI-2K score was completed twice, for a 10- and 30-day window. Forty patients had a classic SLEDAI-2K activity score of 0 and 109 patients had varying levels of disease activity ranging from 1 to 31. In all but one patient, there was agreement between the SLEDAI-2K 10 and 30 days. Thus SLEDAI-2K 30 days is similar to SLEDAI-2K 10 days, both in patients in remission and with a spectrum of disease activity levels. SLEDAI-2K 30 days may now be used to describe disease activity over the previous 30 days.

Genetic complete deficiency of the early complement components such as C1, C2 and C4 commonly results in a monogenetic form of systemic lupus erythematosus (SLE). However, previous studies have examined groups of complete complement deficient subjects for SLE, while a familial SLE cohort has not been studied for deficiencies of complement. Thus, we undertook the present study to determine the frequency of hereditary complete complement deficiencies among families with two or more SLE patients. All SLE patients from 544 such families had CH50 determined. Medical records were examined for past CH50 values. There were 66 individuals in whom all available CH50 values were zero. All but four of these had a SLE-affected relative with a non-zero CH50; thus, these families did not have monogenetic complement deficient related SLE. The four remaining SLE-affected subjects were in fact two sets of siblings in which three of the four SLE patients had onset of disease at <18 years of age. Both patients in one of these families had been determined to have C4 deficiency, while the other family had no clinical diagnosis of complement deficiency. In this second family, one of the SLE patients had had normal C4 and C3 values, indicating that either C1q or C2 deficiency was possible. Thus, only 2 of 544 SLE families had definite or possible complement deficiency; however, 1 of 7 families in which all SLE patients had pediatric onset and 2 of 85 families with at least 1 pediatric-onset SLE patent had complete complement deficiency. SLE is found commonly among families with hereditary complement deficiency but the reverse is not true. Complete complement deficiency is rare among families with two or more SLE patients, but is concentrated among families with onset of SLE prior to age 18.

Complement activation is an important aspect of systemic lupus erythematosus. In this study we investigated the role of C3a/C3a receptor (R) signaling in brains of the lupus model, MRL/lpr mice, by treating the mice with C3aR antagonist (a) from 13 to 19 weeks of age. C3aR mRNA (0.2 ± 0.027 versus 0.56 ± 0.19) and protein (0.16 ± 0.09 versus 0.63 ± 0.19) expression was increased in MRL/lpr brains compared with MRL+/+ controls. Apoptosis, a key feature in lupus brain, was significantly reduced by C3aRa treatment, as assessed by DNA laddering, TUNEL staining and caspase3 activity (48% of MRL/lpr mice). mRNA expression of proinflammatory molecules that cause apoptosis, TNF (0.33 ± 0.07 versus 0.15 ± 0.1), MIP2 (3.8 ± 1.3 versus 1.7 ± 0.6), and INF (4.8 ± 1.0 versus 2.07 ± 1.28) are reduced in MRL/lpr brains with C3aRa treatment. In line with these results, Western blotting demonstrates the significant increase in phosphorylation of survival molecules Akt and Erk, decrease in PTEN and reduced iNOS expression. INF receptor (R) and AMPA-GluR1 co-localized, and concomitant with reduced INFR expression, AMPA-GluR1 expression was also decreased by C3aR antagonist. All of these variables that modulate neuronal excitability and regulate synaptic plasticity are C3aR dependent in the MRL/lpr brains and suggest a potential therapeutic role for C3aR inhibition in CNS lupus.

The objective of this study was to investigate the clinical characteristics and prognosis of Sjögren’s syndrome-onset systemic lupus erythematosus (SS/SLE) patients. Medical charts of 41 consecutive SS/SLE inpatients admitted to Peking Union Medical College Hospital (PUMCH) from February 1998 to February 2008 were systematically reviewed, including demographic data, clinical features, laboratory findings, treatment as well as outcomes. Two hundred and fourteen cases were randomly selected as controls from 2331 SLE-only inpatients treated in PUMCH at the same time period. There were significant differences between SS/SLE and SLE-only patients in the following manifestations (p < 0.05): (1) sex ratio (F/M) (41/0 versus 184/30), age (42.8 ± 41.0 years versus 31.8 ± 31.0 years), disease duration (113.8 ± 84.0 months versus 44.9 ± 18.0 months); (2) clinical features, xerostomia (85.4% versus 6.1%), xerophthalmia (75.6% versus 2.3%), renal tubular acidosis (21.9% versus 0%), interstitial lung disease (12.2% versus 2.8%), facial rash (9.8% versus 46.3%), nephrotic syndrome (7.3% versus 31.3%), central nervous system involvement (4.9% versus 19.6%); (3) laboratory findings, ESR (64.6 ± 75.0 mm/h versus 46.5 ± 34.0 mm/h), C4 (14.8 ± 12.2 g/dl versus 12.0 ± 10.9 g/dl), IgG elevation (56.4% versus 29.9%) and IgA elevation (38.5% versus 20.4%), RF, anti-SSA and anti-SSB positive rates (70.8% versus 20.3%, 82.9% versus 43.4% and 39.0% versus 7.9%); (4) SLEDAI score (8.0 ± 8.0 versus 10.2 ± 10.0), glucocorticoid treatment (methylprednisolone bolus/1–2 mg kg^-1 day^-1 prednisone/<1 mg kg^-1 day^-1 prednisone) (8/26/7 versus 91/102/21), and importantly, rate of death and/or severe irreversible organ failure (2.4% versus 14.9%). SS/SLE patients were followed up for 33.0 ± 34.0 months, 40 cases remained stable at a low dose of corticosteroid. In conclusion, different from SLE-only patients, SS/SLE patients have distinctive clinical manifestations and benign prognosis that require less vigorous treatment with glucocorticoids and/or immunosuppressants.

Severe retinal vasculitis is a rare, but potentially blinding, complication of patients with systemic lupus erythematosus (SLE). We describe here the first reported case of treating severe bilateral SLE-associated retinal vasculitis with the anti-CD20 monoclonal antibody rituximab, a drug which has established its role in rheumatoid arthritis and has shown promise in case series for the treatment of severe SLE that is unresponsive to other therapies. This case suggests that rituximab-induced B-cell depletion may provide an important new therapeutic option for refractory cases of this devastating ocular complication.

Squamous cell carcinoma is a known complication reported to occur in chronic discoid lupus erythematosus in sun-exposed areas. We report a patient with systemic lupus erythematosus who developed a squamous cell carcinoma in a recent plaque of discoid lupus erythematosus in a sun-protected area. This article emphasizes the need for a very high index of suspicion for squamous cell carcinoma and repeated biopsies when discoid lupus erythematosus fails to respond to conventional therapy or there is unexplained exacerbation.

Patients with systemic lupus erythematosus (SLE) are susceptible to the development of lymphoproliferative disorders and postulated causes include intrinsic defects in immune surveillance and iatrogenic administration of immunosuppressants. Since the introduction of mycophenolate mofetil (MMF) to the immunosuppressive regimen for the management of post-organ transplantation, there have been reports of primary lymphoma of the central nervous system (PCNSL). MMF has been widely used to treat active SLE patients with Class IV lupus nephritis. In addition to two previously reported cases of PCNSL among SLE patients on long-term MMF, we report a third patient who has been on treatment with MMF for 8 years. The histology showed features compatible with diffuse large B-cell lymphoma with strong immunohistochemical staining for CD20 and positive signal for Epstein–Barr virus (EBV)-encoded RNA by in-situ hybridization that is similar to other case reports, suggesting EBV driven B-cell lymphoproliferative disease. The patient responded to withdrawal of MMF, intravenous methotrexate, rituximab and whole brain radiotherapy. With the increasing use of MMF in active renal as well as non-renal exacerbations of SLE, PCNSL should be included in the differential diagnosis in patients who present with gradual onset of focal neurological deficit.

Women with antiphospholipid syndrome (APS) may have diverse pregnancy outcomes. The objective of this study was to evaluate pregnancy outcome in women with APS according to their clinical phenotype, i.e. thrombotic and obstetric APS. Eighty-three pregnancies in 67 women with APS were included in the study, including 21 with recurrent miscarriage (Group 1), 21 with late fetal loss or early delivery due to placental dysfunction (Group 2) and 41 with thrombotic APS (Group 3). Group 3 had higher rates of preterm delivery (26.8% versus 4.7%, p = 0.05) than Group 1 and more small for gestational age (SGA) babies than Group 2 (39.5% versus 4.8%, p = 0.003). Group 2 had significantly longer gestations compared with their pretreatment pregnancies (38.4 [28.4–41.4] versus 24.0 [18–35] weeks, p < 0.0001) and 100% live birth rate after treatment with aspirin and low-molecular-weight heparin (LMWH). In conclusion, women with thrombotic APS (Group 3) have higher rates of pregnancy complications than those with obstetric APS (Groups 1 and 2). Treatment with aspirin and LMWH is associated with improved outcomes for women with previous late fetal loss or early delivery due to placental dysfunction (Group 2).

The objective of this study was to determine the vitamin D status and its relationship with disease and therapy features and with bone mineral density in women with systemic lupus erythematosus. Non-pregnant systemic lupus erythematosus women with dual-energy X-ray absorptiometry and vitamin D measurements performed between May 1 2005 and August 31 2006 were studied. In each patient, the lowest T-score of the first dual-energy X-ray absorptiometry scan during the study period was used. In postmenopausal women, a T-score ≥1.0 standard deviation was considered normal, between -1.0 and -2.5 standard deviations osteopenia and ≤2.5 standard deviations osteoporosis; in premenopausal women a T-score ≥2.5 standard deviations was normal and ≤2.5 standard deviations defined as reduced bone density. 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels were determined at the time of dual-energy X-ray absorptiometry. A 25-hydroxyvitamin D level of <80 nmol/L was defined as sub-optimal and a level <40 nmol/L as deficient. Demographic and clinical variables were investigated for association with vitamin D levels by univariate and multivariate analyses. One-hundred and twenty-four systemic lupus erythematosus women had dual-energy X-ray absorptiometry scans and vitamin D assays performed during the study period. Sub-optimal 25-hydroxyvitamin D levels were found in 82 (66.7%) and deficient 25-hydroxyvitamin D levels in 22 (17.9%) patients. The disease-related features examined at the time of vitamin D assays or bone mineral density showed no correlation with vitamin D levels by univariate analyses. Neither 25-hydroxyvitamin D nor 1,25-dihydroxyvitamin D was associated with bone mineral density status among these patients. A multivariate logistic regression model identified season, cumulative glucocorticoid exposure, and serum creatinine as being associated with 25-hydroxyvitamin D levels, whereas ethnicity, glucocorticoid exposure, and serum creatinine were associated with 1,25-dihydroxyvitamin D levels. In conclusion, sub-optimal vitamin D status is common in women with systemic lupus erythematosus and is related to season, cumulative glucocorticoid dose, and serum creatinine.

Infections are an important cause of morbidity and mortality in systemic lupus erythematosus. We aimed to determine the incidence and characteristics of infections in patients hospitalized because of systemic lupus erythematosus, and to identify which factors influence their outcome. The medical records of patients with systemic lupus erythematosus hospitalized between January 2002 and December 2007 were reviewed according to a standardized case form including demographic, clinical, and therapeutic data. The diagnosis of infection was based on clinical findings, the identification of the causative agent or response to antibiotic treatment. The study included 473 patients (mean age 30 ± 11 years; 421 (89%) female) who were hospitalized for a mean of 13 ± 9 days. A community-based infection was suspected in 268 (57%) at admission; the diagnosis was confirmed in 96 patients (22%) and ruled out in 20 (4.2%); nevertheless, 152 patients (32%) received antibiotics on an empirical basis. A nosocomial infection was suspected in 63 (13.3%) of 453 patients and was confirmed in 59 (12.5%). The two most common community-acquired and nosocomial infections affected the respiratory and genitourinary tracts. Gram-negative bacteria were major etiological agents isolated. In the multivariate analysis, community-based infections associated with mucocutaneous, renal, or central nervous system disease activity as well as fever, and Mex-SLEDAI at admission and nosocomial infections to azathioprine use, infection at admission, disease duration, and hospitalization >7 days. We conclude that infections are an important cause of hospitalization of systemic lupus erythematosus patients. Risk factors include disease activity, use of immunosuppressants, disease duration, and length of hospital stay.

Systemic vasculitis is a known complication of patients with systemic lupus erythematosus (SLE). Inflammation of the vessels can result in the development of arterial aneurysms with a potential risk of rupture or bleeding. Case history: We present the case of a 56-year-old woman with SLE who developed three episodes of gastrointestinal (GI) bleeding without evidence of lesions in the GI tract. Multiple aneurysms of the hepatic artery were identified and treated with endovascular embolization, with no further GI bleeding. After embolization, the patient developed multiple bilomas that required percutaneous drainage, and subsequent abscesses which eventually resolved without further complications. Conclusion: Hepatic aneurysms, possibly secondary to vasculitis, may cause GI bleeding, and should be suspected in patients with SLE and GI bleeding with no apparent cause identifiable through standard endoscopy of the upper and lower GI tract.

A 48-year-old woman presented with isolated sixth cranial nerve palsy. She subsequently developed systemic lupus erythematosus (SLE) based on clinical and laboratory parameters. Three years later, she presented again with sixth cranial nerve palsy affecting the contralateral eye. Within 2 weeks of steroid initiation, complete recovery occurred. The unusual rare presentation of SLE in the current patient, as well as the pathogenesis and treatment of cranial neuropathy in SLE are discussed.

Combined central retinal artery occlusion and central retinal venous occlusion have been rarely reported in patients with systemic lupus erythematosus and anti-phospholipid syndrome. The impact of this severe vaso-occlusive disease on vision is usually devastating and permanent in spite of vigorous treatment. We report herein a 35-year-old female patient displaying a transient and reversible process. Her best-corrected visual acuity improved from 6/60 to 6/8.6 1 day later, before the initiation of systemic corticosteroid and anti-coagulant treatment. The retina regained a normal appearance with her vision recovering to 6/6 2 weeks after the episode of temporary vision loss. Her rapid recovery suggests that continued anti-coagulation therapy and close follow-up to prevent severe complications and recurrent thrombosis is warranted.

Patients with systemic lupus erythematosus often assess their disease activity differently from their physicians. We studied the factors associated with this discordance. The data provided by 534 systemic lupus erythematosus patients were analyzed. We compared the physician and patient assessments of lupus activity on a visual-assessment scale from the same visit. We collected clinical data and scores from MOS 36-Item Short-Form Health Survey, Systemic Lupus Erythematosus Quality-of-Life Questionnaire, Rheumatology Attitudes Index, Systemic Lupus Erythematosus Disease Activity Index, and revised Systemic Lupus Activity Measure. Patients tended to score their disease activity higher than do their physicians, when these factors were present: poorer general health assessment, presence of thrombocytopenia, hypertension and urinary sediments, and difficulty in carrying groceries. Physicians tended to score the disease activity higher than do the patients in these circumstances proteinuria, hemolysis, use of azathioprine or cyclophosphamide, tiredness, photosensitivity, higher revised Systemic Lupus Activity Measure score, casturia, and patient report of being more easily ill than are other patients. There was only moderate correlation between the discordance in the baseline and the subsequent visits. The physician assessment of disease activity at baseline correlated better with an objective measure of disease activity (revised Systemic Lupus Activity Measure) in the subsequent visit than the patient assessment. In conclusion, discordance in the perception of disease activity between patients and physicians may be amenable to intervention.

Cardiovascular disease risk is increased in individuals suffering from systemic lupus erythematosus. Understanding the mechanism(s) of systemic lupus erythematosus-accelerated atherosclerosis is critical for the development of effective therapies. Our laboratory previously demonstrated that radiation chimeras of systemic lupus erythematosus-susceptible B6.Sle1.2.3 and low density lipoprotein receptor (LDLr)^–/– mice have augmented atherosclerosis, which is associated with increased T-cell burden and activation in the lesion. The goals of this study were to further define specific immune mechanisms that mediate accelerated atherosclerosis and to determine whether the gene interval Sle3, which is linked to lupus-associated T-cell dysregulation, was sufficient to modulate atherogenesis. We transferred B6.Sle3 or C57Bl/6-derived bone marrow cells into lethally irradiated LDLr^–/– mice (hereafter referred to as LDLr.Sle3 and LDLr.B6, respectively). Sixteen weeks after transplantation, the mice were placed on a western-type diet for 8 weeks. Our analyses revealed that LDLr.Sle3 mice had increased auto-antibody production against double-stranded DNA and cardiolipin compared with LDLr.B6 controls. We also found an increase in atherosclerosis-associated oxLDL antibodies. Antibody isotypes and serum cytokine analysis suggested that the humoral immune response in LDLr.Sle3 mice was skewed toward a Th2 phenotype. This finding is consistent with lupus-associated immune dysregulation. Additionally, LDLr.Sle3 mice had decreased serum cholesterol and triglyceride levels. However, there was no difference in lesion area or cellular composition of lesions between the two groups. These data demonstrate that, despite no change in lesion area, transfer of Sle3-associated T-cell dysregulation alone to LDLr-deficient mice is sufficient to decrease serum cholesterol and to exacerbate humoral immune responses that are frequently associated with atherosclerosis.

Diagnosing vulvar intraepithelial neoplasia in a young woman presenting mainly with skin manifestations of lupus and with no other risk factors is a major challenge. The case of a 27-year-old woman with systemic lupus erythematosus and vulvar intraepithelial neoplasia is described. Although progression of vulvar intraepithelial neoplasia to invasive planocellular carcinoma is rare, prompt and adequate diagnosis and treatment will help ensure the best possible quality of life.