Use of belimumab throughout pregnancy to treat active systemic lupus erythematosus—A case report

Background

Pregnancy can lead to flares in systemic lupus erythematosus (SLE), and the presence of SLE in pregnancy could lead to a poor outcome for the mother and the fetus.

Objective

To describe a patient whose active SLE (including lupus nephritis) was managed with the use of belimumab throughout pregnancy.

Methods

A case report and review of relevant literature is presented.

Results

A 38-year-old Caucasian woman with SLE was seen for advice regarding planning a pregnancy and management of her active lupus (cutaneous lupus, angioedema, lupus nephritis, leukopenia, and anti-phospholipid antibody syndrome) that could only be controlled by mycophenolate, a drug contraindicated in pregnancy. Azathioprine, hydroxychloroquine, rituximab, and moderate doses of prednisone were either unable to control her disease or led to unacceptable toxicity. After detailed discussions, she was treated with belimumab, which controlled her SLE and allowed withdrawal of mycophenolate. Belimumab was continued throughout the pregnancy, leading to well-controlled SLE and uneventful course, albeit with the presence of mild Ebstein?s anomaly in the baby.

Conclusion

To our knowledge, this is the first case report of belimumab use throughout pregnancy for controlling active SLE. Data from the belimumab pregnancy registry would be useful to confirm our findings and to further assess safety of this agent for use in pregnancy.     

Are RASopathies new monogenic predisposing conditions to the development of systemic lupus erythematosus? Case report and systematic review of the literature

Objective

RASopathies (Noonan syndrome (NS) and Noonan-related syndromes) are neurodevelopmental syndromes resulting from germline mutations in genes that participate in the rat sarcoma/mitogen-activated protein kinases (RAS/MAPK) pathway (PTPN11, SOS1, RAF, KRAS or NRAS, and SHOC2). Some monogenic conditions are associated with the development of systemic lupus erythematosus (SLE), and a few reports described the association of SLE with NS. We aim to search for a relationship between RASopathy and the development of SLE.

Methods

We reported for the first time a case of 13-year-old boy with NS with loose anagen hair (NSLAH) resulting from mutation in SHOC2 who developed an autoimmune disorder that fulfilled four American College of Rheumatology (ACR) criteria for the classification of SLE (polyarthritis, pericarditis, antinuclear antibodies, and anti-DNA antibodies). The case report then prompted a literature review by a systematic search for English and French articles on the subjects of RASopathies and SLE that had English abstracts in PubMed from 1966 to 2012.

Results

We identified seven additional patients with RASopathy and SLE. The male-to-female ratio was 1:1 and age at onset of SLE ranged from 5 to 32 years. The most common features were polyarthritis (7/8 patients), autoimmune cytopenia (4/8 patients), and pericarditis (4/8 patients) while only one patient presented with skin involvement.

Conclusion

The association of two rare diseases in eight patients suggests that RASopathies may be associated with the development of SLE, which is characterized by a higher male-to-female ratio, a lower rate of skin involvement, and a higher rate of pericarditis than “classic” SLE.     

Tocilizumab for polymyalgia rheumatica: Report of two cases and review of the literature

Background

Glucocorticoids (GC) are the mainstay of treatment of polymyalgia rheumatica (PMR). However GC-related adverse events occur frequently, particularly in patients with relapsing disease. Several studies have demonstrated that IL-6 is a key player in the pathogenesis of PMR.

Objectives

To report 2 patients with PMR treated with the anti-IL-6 receptor monoclonal antibody tocilizumab (TCZ) and to review the published evidence on the efficacy and safety of TCZ in patients with PMR.

Methods

We treated 2 GC-naive patients with newly diagnosed pure PMR with monthly TCZ infusions (8 mg/kg body weight) for 6 months. Disease activity and drug tolerability were assessed clinically, by laboratory tests, and bilateral shoulder ultrasonography before starting the treatment and subsequently every month during TCZ therapy. We performed a systematic literature search (PubMed until July 2012) using the terms “tocilizumab,” “anti-IL-6-receptor,” “polymyalgia rheumatica,” “giant cell arteritis”, and “large-vessel vasculitis” to identify published reports of patients with PMR treated with TCZ.

Results

One of our patients responded well to TCZ, while the other patient required GC therapy after the 2nd TCZ infusion because of lack of appreciable clinical response. Both patients tolerated TCZ well. The review of the literature revealed 4 reports with a total of 9 patients who received TCZ for PMR. In 7 of these 9 patients, PMR was associated with giant cell arteritis. Including our patients, 5 patients received TCZ alone and 6 TCZ plus GC. A good response to TCZ treatment was observed in all patients reported in the literature without any major adverse events.

Conclusions

TCZ both as monotherapy and in association with GC appears to be mostly effective and safe to treat patients with PMR. However, larger controlled studies are required to confirm these favorable data.     

Coût du lupus systémique en France des patients adultes avec une maladie active et traitée (étude LUCIE)

Purpose

To evaluate in France the annual direct medical cost of adult patients with active systemic lupus erythematosus (SLE) on medication and estimate the cost of a flare.

Methods

A two-year, observational, retrospective, multicenter study, carried out between December 2010 and February 2011. Patients’ characteristics, SLE disease activity and severity, rate of flares, healthcare consumption (medications, hospitalisations, etc.) were evaluated. Medical costs were assessed from the national Health Insurance perspective. Cost predictors were estimated using multivariate regression models.

Results

Eight centres specialized in SLE management included 93 eligible patients (including 50.5% severe). The mean age was 39.9 (11.9) years and 93.5% were women. At baseline, the mean SLE duration was 9.8 (6.6) years. The mean scores of the SELENA-SLEDAI instrument and the SLICC/ACR index were higher in severe patients (9.8 vs 5.6, and 1.2 vs 0.4 respectively; P < 0.001). Over the study period, 51% of patients received the combination containing at least corticosteroids or immunosuppressants. The mean annual direct medical cost of severe patients was €4660 versus €3560 for non-severe patients (non-significant difference). The cost of medications (61.8% of the annual cost) was higher in severe patients (€3214 vs €1856; P < 0.05). Immunosuppressants and biologics represented 26.5% and 4.6% of the annual total cost respectively. Patients experienced on average 1.10 (0.59) flares/year, of which 0.50 were severe flare. The occurrence of a new severe flare incremented the annual cost of €1330 (P < 0.05).

Conclusion

Medications represented the major component of the annual direct medical cost. Severe flares increase significantly the cost of SLE care management.     

Epigenetics and methylation in the rheumatic diseases

Objectives

Rheumatic diseases encompass a wide range of conditions of poorly characterized etiopathology, many having both genetic and environmental susceptibility factors. Epigenetic studies are providing new insights into disease pathogenesis. Recent rheumatology literature related to DNA methylation studies—both epigenome-wide and candidate gene—are discussed, as well as methodological issues.

Method

A PubMed search for articles published until April 2013 was conducted using the following keywords: (“methylation” OR “epigenetics”) AND (“rheumatoid arthritis” OR “lupus” OR “autoimmune disease” OR “osteoporosis” OR “osteoarthritis” OR “musculoskeletal disorder”) and EWAS. The reference lists of identified articles were searched for further articles.

Results

Several genome-wide methylation studies have been reported recently, mostly in autoimmune rheumatic diseases. Overall, these studies have identified methylation signatures in disease, clustering of subgroups as well as new and known epigenetic associations. Methodological issues, small sample sizes and reduced coverage of methylation assays render many results preliminary.

Conclusions

There have been a number of epigenetic advances in rheumatic diseases recently. The new technologies and emerging field of epigenome-wide association will provide novel perspectives in disease etiology, diagnosis, classification, and therapy.     

Risk of coronary artery disease in patients with idiopathic inflammatory myopathies: A systematic review and meta-analysis of observational studies

Objectives

To investigate the risk of coronary artery disease in patients with idiopathic inflammatory myopathies (IIM).

Methods

We conducted a systematic review and meta-analysis of observational studies that reported odds ratios, relative risks, hazard ratios, or standardized incidence ratios comparing the risk of coronary artery disease in patients with IIM versus non-IIM participants. We searched published studies indexed in MEDLINE, EMBASE, and the Cochrane database from inception to December 2013 using the terms “coronary artery disease” OR “coronary heart disease” OR “myocardial infarction” OR “atherosclerosis” combined with the terms “dermatomyositis” OR “polymyositis” OR “Idiopathic inflammatory myopathy.” Pooled risk ratio and 95% confidence interval were calculated using a random-effect, generic inverse variance method.

Result

Overall, four studies were identified and included for data analysis. The pooled risk ratio of CAD in patients with IIM was 2.24 (95% CI: 1.02–4.92). The statistical heterogeneity of this meta-analysis was high with an I² of 97%.

Conclusion

Our study demonstrated a statistically significant increased risk of CAD among patients with IIM.     

Do current arterial hypertension treatment guidelines apply to systemic lupus erythematosus patients? A critical appraisal

Objective

Arterial hypertension (HTN) is reported to burden up to 74% of systemic lupus erythematosus (SLE) patients and contributes significantly to accelerated atherosclerosis and increased cardiovascular (CV) risk. Current HTN treatment guidelines have not incorporated lupus patients in their recommendations; whether these guidelines can be fully implemented in SLE is doubtful.

Methods

A critical appraisal of the existing HTN guidelines in regard to SLE is presented in this review, based upon clinical and experimental data. Particular issues addressed are the time of antihypertensive therapy initiation, the optimal blood pressure level, the antihypertensive agent of first-choice and the need for reduction of the total cardiovascular risk in SLE.

Results

Antihypertensive therapy should be recommended at levels of 140/90 mmHg (systolic and diastolic BP, respectively) in newly diagnosed lupus patients without overt target organ involvement. In the case of lupus nephritis (LN) or diabetes mellitus (DM), therapy should be implemented at lower levels, such as 130/80 mmHg. Hypertensive lupus patients should be considered at high or very high CV risk and, consequently, the optimal BP level should be less than 130/80 mmHg. Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) seem to be a safe and efficacious first-choice antihypertensive treatment in lupus patients. Total CV risk should be considered and co-morbidities (dyslipidemia, antiphospholipid syndrome, etc.) should be managed promptly.

Conclusions

Current HTN therapeutic guidelines, lacking data from large-scale clinical trials, may not adequately apply to SLE patients. The assessment of the aforementioned recommendations in randomized clinical trials is expected to confirm their value in reducing CV risk in SLE.     

La pancréatite lupique : une série de six cas

Purpose

The occurrence of acute pancreatitis in systemic lupus erythematosus (SLE) is known but rare, and is exceptionally the presenting manifestation. Its pathogenesis is multifactorial, and it is difficult to separate what belongs to vasculitis, thrombotic phenomena in the context of an associated antiphospholipid syndrome, or iatrogenic complications. We report on six cases of lupus pancreatitis.

Methods

This is a retrospective monocenter study of 110 patients with SLE. The diagnosis of lupus pancreatitis was established after exclusion of other causes of pancreatitis.

Results

Five women and one man (5.4%) with a mean age of 36.3 years presented with lupus pancreatitis. In four patients the pancreatitis was concurrent with the diagnosis of SLE and it occurred later during an exacerbation of the disease in the two remaining patients. In all patients, pancreatic manifestations were associated with other organ involvement. Clinical manifestations were: abdominal pain (n = 6), vomiting (n = 3), and fever (n = 3). Elevated pancreatic enzyme was noted in all cases. All patients were treated by high doses of glucocorticoids. The outcome was favorable in five patients, and one patient died.

Conclusion

Pancreatitis may be the presenting manifestation of SLE. Its pathogenesis is often multifactorial. The outcome is usually favorable with corticosteroids.     

Response of QT interval in methadone maintenance treated patients to the rapid changes in heart rate provoked by brisk standing: Comparison to healthy controls and patients with long QT syndrome

Background

Patients on methadone maintenance therapy are somehow similar to patients with congenital long QT syndrome (LQTS) because they have malfunction of potassium channels caused by a drug that cannot be easily discontinued. We tested patients on methadone therapy with the “stand-up” test, which has been shown to unravel pathologic QT-prolongation in congenital long-QT patients.

Methods

“Stand-up” test results of methadone-users, healthy volunteers and congenital LQTS patients were compared. Methadone serum levels and doses were collected. The prognostic value of the test was evaluated after 4 years of follow-up.

Results

The QT-response of methadone-users to the “stand-up” test resembled that of healthy volunteers more than the response of LQTS-patients. Differences in the QTc of methadone treated patients and controls, which were statistically significant at baseline, became no longer significant after standing. Within 52 months of follow-up, one patient had suffered unexplained death and one had documented ventricular tachycardia.

Conclusions

The QT-response of methadone-users to the “stand-up” test is similar to that of healthy volunteers, not to that of LQTS-patients.     

Relative's experiences before and after a heart or lung transplantation

Background

Relatives take on great responsibilities during patients' heart or lung transplant process and an understanding for their situation is required.

Objective

To describe relative's experiences before and during the patient's hospital stay as well as during the first 6 months after a heart or lung transplantation.

Methods

Using qualitative content analysis, 15 relatives (eight women and seven men) aged 36–65 years were interviewed within 6 months of a heart or lung transplantation.

Result

Three categories that illuminate relatives' experiences have been identified: “Navigate specific circumstances,” “Facilitate throughout the transplantation journey” and “Experiences of strength and weakness of information and support.” The relatives reported involvement in the transplantation decision, peer support, information seeking, burden and coping.

Conclusion

Greater awareness about relatives' experiences with identification of appropriate support and information exchange between health care professionals and relatives is important. This awareness could provide benefits for heart or lung transplant patients, families and health care organizations.     

A regulatory role for CD72 expression on B cells in systemic lupus erythematosus

Background

B regulatory cells and their regulatory products/markers, such us semaphorin 3A (sema3A) and its receptor NP-1, FcγIIB, IL-10, and others, act at the very base of self-tolerance, maintenance, and prevention of autoimmune disease development.

Objectives

The aim of the present study was to assess the involvement of CD72, a regulatory receptor on B cells, in systemic lupus erythematosus (SLE). In addition, the potential of soluble sema3A in enhancing the expression of CD72 on B cells of SLE patients was investigated.

Results

CD72 expression on activated B cells of SLE patients was significantly lower than that of normal controls. This lower expression of CD72 in SLE patients correlated inversely with SLE disease activity and was associated with lupus nephritis, the presence of anti-dsDNA antibodies, and low levels of complement. Co-culture of purified B cells from healthy controls with condition-media containing recombinant sema3A resulted in significant enhancement of CD72. Similar enhancement of CD72 on activated B cells from SLE patients, though significant, was still lower than in normal individuals.

Conclusions

The lower expression of CD72 on activated B cells from SLE patients correlates with SLE disease activity, lupus nephritis, the presence of anti-dsDNA antibodies, and low levels of complement. The improvement of CD72 expression following the addition of soluble semaphorin 3A suggests that CD72 may be useful as a biomarker to be followed during the treatment of SLE.     

Intensity of peri-operative glycemic control and postoperative outcomes in patients with diabetes: a meta-analysis

Aims

Peri-operative hyperglycemia is a risk factor for postoperative morbidity and mortality. However, the role of specific glycemic targets in reducing this risk has not been defined, particularly among patients with diabetes. Thus, our objective was to conduct a meta-analysis relating distinct peri-operative glycemic targets and postoperative outcomes in patients with diabetes.

Methods

A systematic review was performed by two authors utilizing pre-specified terms: “diabetes mellitus” and “perioperative” and “mortality” and “blood glucose” or “strict glucose control” or “intensive insulin therapy” in PUBMED, CENTRAL and EMBASE. Glycemic control was considered strict when perioperative targets ranged between 100 and 150 mg/dL (5.6–8.3 mmol/l), moderate when the targets ranged between 150 and 200 mg/dL 8.3–11.1 mmol/l), and liberal when the target was >200 mg/dL (11.1 mmol/l). The data were combined utilizing the Dersimoan–Laird random-effects method. The primary endpoint was postoperative mortality with secondary endpoints of postoperative atrial fibrillation, wound infection, and stroke.

Results

The literature search yielded 760 studies, of which only 6 met inclusion criteria. When compared with a liberal target, pooled data showed that a moderate glycemic target was associated with reduced postoperative mortality (OR = 0.48, 95% CI 0.24–0.76) and stroke (OR = 0.61, 95% CI 0.38–0.98), but no differences in atrial fibrillation or wound infection were found. There were no significant differences in postoperative outcomes between moderate versus strict perioperative glycemic target.

Conclusions

Pooled results suggest that in patients with diabetes, a moderate peri-operative glycemic target (150–200 mg/dl [5.6–8.3 mmol/l]) is associated with reduction in postoperative mortality and stroke compared with a liberal target (>200 mg/dl [11.1 mmol/l]), whereas no significant additional benefit was found with more strict glycemic control (<150 mg/dl [5.6 mmol/l]).     

Five year time course of celiac disease serology during gluten free diet: results of a community based “CD-Watch” program

Background

Little information is available on the effect of a follow-up strategy in celiac disease patients during gluten-free diet.

Aims

To assess 5 year time course of t-transglutaminase antibodies (t-TG) in celiac disease patients enrolled in a community based follow-up program.

Methods

Annual t-TG testing and periodical clinic visit in 2245 patients.

Results

Proportion of patients with negative t-TG progressively increased from 83% to 93% during the 5-year follow-up: poor adherence to gluten-free diet (HR 4.764), long duration of gluten-free diet (HR 0.929) and female gender (HR 1.472) were independently associated with serological outcome. In individual patients, 69% tested t-TG “persistently negative”, 1% “persistently positive” and 30% “intermittently negative or positive”. By applying mathematical modelling to t-TG conversion rates observed in this latter group at beginning and end of the follow-up program, the predicted proportion of t-TG negative population increased from 90% to 95% over 5 years.

Conclusions

Time-course of t-TG serology in the community fluctuates in 1/3 of celiac disease patients suggesting inconstant adherence to gluten-free diet and need of follow-up strategy. Periodical serological and clinical follow-up is a viable and efficacious strategy to promote adherence to gluten-free diet as inferred from time-course of t-TG serology.     

Management and timing of access-site vascular complications occurring after trans-radial percutaneous coronary procedures

Background

Access-site vascular complications (ASVC) in patients undergoing trans-radial coronary procedures are rare but may have relevant clinical consequences. Data regarding the optimal management of radial-access-related ASVC are lacking.

Methods

During a period of 6 years we prospectively collected ASVC. ASVC were defined as any complication requiring ultrasound examination or upper limb angiography. ASVC were categorized according to the timing of diagnosis: “very early” (in the cath lab), “early” (after cath lab discharge, but during the hospital stay) and “late” (after hospital discharge). The need of surgery (primary end-point) and the development of neurological hand deficit (secondary end-point) were assessed.

Results

Fifty-seven radial-artery related ASVC were collected. ASVC diagnosis was obtained by upper limb angiography in 25 patients (44%) and by Doppler in 32 patients (56%). Surgery was required in 6 cases (11%), the remaining patients receiving successful conservative management (which included prolonged local compression). Three patients (who received surgery) exhibited a mild neurological hand deficit in the follow-up. Need for surgery differed significantly according to timing of diagnosis as it occurred in 1 of 26 patients (3.8%) with “very early” diagnosis, in 1 of 21 patients (4.8%) with “early” diagnosis, and in 4 of 10 patients (40%) with “late” diagnosis (p = 0.026).

Conclusions

ASVC are diagnosed with different timing after trans-radial procedures. Conservative management including local compression allows successful management in the majority of ASVC. Prompt recognition is pivotal as late diagnosis is associated to the need for surgery.     

The Systemic Lupus International Collaborating Clinics (SLICC) damage index: A systematic literature review

Objectives

We performed a systematic literature review to determine factors that influence damage and damage progression in SLE patients and how damage relates to mortality in this population.

Methods

A search of Medline, Embase and Web of Science was performed, with papers included if they met the requirements of containing keywords relating to SLE and damage assessment using the SDI, published between 1990 and October 2012.

Results

A total of 358 articles were identified, with 50 included in this review. From 17 studies reporting damage at more than 2 time points, damage progressed over time, but the rate of damage accrual reported was variable across studies. Demographic factors that influence the accrual of damage in several reports include male gender, older age, longer disease duration, Afro-Caribbean and Indo-Asian ethnicity. Patients with higher disease activity at a single time point or over time accrue greater damage. Certain organ system involvement also predicts damage accrual, in particular renal and neuropsychiatric involvement. Corticosteroids, cyclophosphamide and azathioprine all show an association with damage accrual, while hydroxychloroquine appears to have a “protective” effect. Four studies, which examined prognosis, all demonstrated that damage is a predictor of future mortality.

Conclusions

Damage in SLE patients increases over time and predicts future mortality. Patients at risk of damage can be identified from demographics factors and the pattern of clinical involvement. Disease activity, corticosteroids and immunosuppressive therapy are also associated with future damage but further studies are needed to separate the mechanisms of these associations from the problem of residual confounding.     

Non-length-dependent and length-dependent small-fiber neuropathies associated with tumor necrosis factor (TNF)-inhibitor therapy in patients with rheumatoid arthritis: Expanding the spectrum of neurological disease associated with TNF-inhibitors

Objective

Small-fiber neuropathy causes severe burning pain, requires diagnostic approaches such as skin biopsy, and encompasses two subtypes based on distribution of neuropathic pain. Such biopsy-proven subtypes of small-fiber neuropathies have not been previously described as complications of tumor necrosis factor (TNF)-inhibitor therapy.

Methods

We therefore characterized clinical and skin biopsy findings in three rheumatoid arthritis (RA) patients who developed small-fiber neuropathies associated with TNF-inhibitors. We also conducted a systematic review of the literature to characterize subtypes of neuropathies previously reported in association with TNF-inhibitor therapy.

Results

Two patients presented with a “non-length-dependent” small-fiber neuropathy, experiencing unorthodox patterns of burning pain affecting the face, torso, and proximal extremities. Abnormal skin biopsy findings were limited to the proximal thigh, which is a marker of proximal-most dorsal root ganglia degeneration. In contrast, one patient presented with a “length-dependent” small-fiber neuropathy, experiencing burning pain only in the feet. Abnormal skin biopsy findings were limited to the distal feet, which is a marker of distal-most axonal degeneration. One patient developed a small-fiber neuropathy in the context of TNF-inhibitor-induced lupus. In all patients, neuropathies occurred during TNF-inhibitor-induced remission of RA disease activity and improved on withdrawal of TNF-inhibitors.

Conclusions

We describe a spectrum of small-fiber neuropathies not previously reported in association with TNF-inhibitor therapy, with clinical and skin biopsy findings suggestive of dorsal root ganglia as well as axonal degeneration. The development of small-fiber neuropathies during inactive joint disease and improvement of neuropathic pain upon withdrawal of TNF-inhibitor suggest a causative role of TNF-inhibitors.     

Coexistence of systemic lupus erythematosus and multiple sclerosis: Prevalence,clinical characteristics,and natural history

Objectives

The coexistence of systemic lupus erythematosus (SLE) and multiple sclerosis (MS) in the same individual has rarely been described. Our objective was to report on the prevalence, clinical characteristics, and prognosis of cases fulfilling the criteria for both SLE and MS.

Methods

We utilized existing patient cohorts from the Departments of Rheumatology and Neurology, University of Crete, and screened patients diagnosed with either SLE (n = 728) or MS (n = 819) for features of both diseases. The clinical, laboratory, and neuroimaging findings were assessed.

Results

We identified nine patients who fulfilled the diagnostic criteria for both SLE and MS, corresponding to a prevalence rate of 1.0–1.2% in each cohort. All patients were women, with an average age at SLE diagnosis of 42.1 years (range: 34–56 years). The diagnosis of SLE preceded the development of MS in five patients, with a time lag ≤5 years in four of them. Initial presentation of MS included spinal symptoms in seven patients. All patients had features of mild SLE with predominantly cutaneous, mucosal, and musculoskeletal manifestations. Accordingly, therapeutic decisions were mainly guided by the severity of the neurological syndrome. During the median follow-up of 4 years (range: 1–10 years), three patients remained stable and the remaining experienced gradual deterioration in their neurological status. SLE remained quiescent in all patients while on standard immunomodulatory MS therapy.

Conclusions

Occurrence of both diseases in the same individual is rare, corroborating data that suggest distinct molecular signatures. SLE and MS coexistence was not associated with a severe phenotype for either entity.     

The epidemiology of atherosclerotic cardiovascular disease among patients with SLE: A systematic review

Objective

To perform a systematic review of the literature regarding the epidemiology of the association between systemic lupus erythematosus (SLE) and atherosclerotic cardiovascular disease (CVD), including the increased risk for CVD, as well as the risk factors responsible for development of CVD in patients with SLE.

Methods

We followed the PRISMA guidelines to systematically search the PubMed database from inception to June 2012. Studies were selected using predefined eligibility criteria, and 2 authors independently extracted data. The risk of bias was measured for each study using a domain-based assessment.

Results

We report on 28 studies that met criteria for inclusion in our analysis. We found strong epidemiologic evidence that SLE patients have an increased relative risk of CVD compared to controls. There is limited information regarding relative CVD mortality risks among SLE patients. Traditional CVD risk factors, including age, male sex, hyperlipidemia, smoking, hypertension, and CRP, are associated with CVD risk among SLE patients. Several SLE-specific factors, including disease activity and duration, and possibly specific manifestations and therapies, further increase risk. Several risk factors, such as disease activity and glucocorticoid use, are closely associated, making it difficult to disentangle their effects.

Conclusions

CVD risk among SLE patients compared to the general population is at least doubled. While older SLE patients appear to have the highest absolute risks of CVD, young women have alarmingly high relative risks, given the rarity of CVD in the comparison general population. Both traditional and SLE-specific risk factors are important, although there are discrepancies within the literature.