Criteria For Systemic Lupus Erythematosus Research Articles

A review and meta-analysis of anti-ribosomal P autoantibodies in systemic lupus erythematosus.

The discovery of autoantibodies to ribosomal proteins (anti-RibP) dates back more than fifty years when antibodies to ribosomes were identified in systemic lupus erythematosus (SLE) sera. Over the years, anti-RibP autoantibodies have been the subject of extensive study and became known as a highly specific biomarker for the diagnosis of SLE and were associated with neuropsychiatric SLE (NPSLE), lupus nephritis (LN) and hepatitis (LH). As demonstrated by studies on cultured human cells and of murine models, there is evidence to suggest that anti-RibP may have a pathogenic role in LN and NPSLE. Despite a wealth of evidence, in comparison to other SLE autoantibodies such as anti-Sm and anti-dsDNA, anti-RibP has not been included in classification criteria for SLE. A significant challenge is the variability of assays used to detect anti-RibP, including the antigens and diagnostic platforms employed. This may account for the marked variation in frequencies (10-47%) in SLE and its association with clinical and demographic features reported in SLE cohorts. We performed a systematic literature review and meta-analysis to help clarify its prevalence, various clinical and serological associations in SLE based on the different RibP antigens and assay platforms used.

Systemic lupus erythematosus in the setting of HIV-1 infection: a longitudinal analysis.

Patients with concomitant HIV-1 infection and systemic lupus erythematosus (SLE) followed longitudinally at an HIV outpatient clinic from 1994 to 2019 were examined. Patients met 1982 and 1997 ACR classification criteria for SLE at the Thomas Street clinic from 1994 to 2019. Clinical and demographic comparisons were made with a non HIV-SLE patient cohort, the Lupus in Minorities Studies, Nature versus Nurture (LUMINA) study. Twenty-two patients with concomitant HIV-1 infection and SLE were identified, including 18 females, 3 males, and 1 male to female transgender. Overall, 81.8% of SLE-HIV patients were African-American compared to 55.3% of the 5856 patients seen at the HIV clinic from 2016 to 2017 (p= 0.02, OR = 3.6). There were 12 patients that developed HIV-1 in the setting of SLE and 10 patients that developed SLE in the setting HIV-1. This demographic distribution was significant when compared with the 1604 unique patients in the HIV rheumatology clinic from 1994 to 2019 (p= 0.03, OR = 5.9) and also significant when compared with the 5856 patients attending the county HIV clinic overall in 2016-2017 (p= 0.008, OR = 7.2). When comparing with the non-HIV SLE cohort, anti-dsDNA antibodies were noted less frequently in all HIV-SLE patients (p= 0.0002) including all sub-cohorts of our patients. Skin/mucosal involvement (p= 0.0003) and cytopenias (p= 0.0001) occurred less frequently in the patients that were diagnosed with HIV after their SLE diagnosis compared to non-HIV SLE patients. In a large county HIV clinic setting, the prevalence of SLE was significantly higher in African American women. Anti-dsDNA antibodies were less frequent in HIV-1 positive SLE patients.Key Points• This paper presents clinical and laboratory data on the largest cohort of SLE patients with HIV-1 infection reported to date.• The prevalence of SLE in a large outpatient HIV-1 clinic was larger than reported in HIV negative population studies.• The prevalence of SLE was particularly high in black HIV-1 infected women.• Skin/mucosal involvement and anti-ds DNA antibodies were less common in patients with HIV-1 and SLE compared to patients with SLE without SLE>.

Kikuchi-Fujimoto disease preceded by lupus erythematosus panniculitis: do these findings together herald the onset of systemic lupus erythematosus?

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare disorder that must be distinguished from systemic lupus erythematosus (SLE). Although a minority of patients with KFD develop SLE, most patients have a self-limited disease. Importantly, KFD can have skin manifestations resembling cutaneous lupus. Therefore, the diagnosis of SLE should be predicated on a complete rheumatologic workup and not on the constellation of skin disease and lymphadenitis. Nonetheless, as our exceedingly rare case illustrates, patients who do not initially meet diagnostic criteria for SLE require dermatologic follow-up. We present a young adult woman who had a remote history of KFD and later presented with combined features of discoid lupus and lupus erythematosus panniculitis (LEP). On subsequent rheumatologic workup, she fulfilled criteria for SLE. We discuss the differential diagnosis of both KFD and LEP and emphasize how strong communication among dermatologists and other healthcare providers is essential in the management of patients with KFD.

Lupus anticoagulant- hypoprothrombinemia syndrome detected in a patient with systemic lupus erythematosus with lupus nephritis

Systemic lupus erythematosus is well known to cause renal and haematological manifestations. Here we present a young female presenting with nephrotic syndrome fulfilling criteria for systemic lupus erythematosus found to have lupus anticoagulant hypoprothrombinemia syndrome on the evaluation for deranged coagulation profile. Prompt immunosuppressive therapy resulted in both renal and haematological resolution.

Seronegative Lupus- A Wolf in Sheep’s Skin

Systemic Lupus Erythematosus (SLE) is a chronic inflammatory multisystem autoimmune disease. Most of the SLE cases are seropositive, but rare (5%) seronegative SLE cases can also present with complications. Hepatic involvement SLE is multifactorial like hepatotoxic drugs, steatohepatitis, viral hepatitis and Autoimmune Hepatitis (AIH). However, the differentiation between lupus-related hepatitis and AIH remains a challenge to the clinician because of many similar features. It is very difficult to differentiate whether hepatitis is due to autoimmune involvement or purely lupus related on the basis of clinical and biochemical parameters. The patient must fulfill ACR criteria for SLE and International Autoimmune Hepatitis Group (IAIHG) criteria for AIH. Histological diagnosis is considered to be definative in differentiating SLE-related hepatitis and AIH. The cardiac manifestations of SLE are multiple with pericardial disease being the most common. While pericardial effusion is rarely haemodynamically significant, the occurrence of subsequent constrictive pericarditis is even less frequent with only occasional reports in the literature. Authors described a case of a 17-year-old female with Antinuclear Antibody (ANA) negative active SLE (seronegative) with AIH and constrictive pericarditis. The patient responded well to the conservative management initially but later developed drug induced myelosuppression and bilateral pneumonia and succumbed.

Clinicopathological and Immunological Profile of Patients with Cutaneous Manifestations and their Relationship with Organ Involvement in Systemic Lupus Erythematosus Attending a Tertiary Care Center of Eastern India.

Background:Lupus erythematosus (LE) is an autoimmune disorder with diverse clinical manifestations ranging from mild cutaneous disorder to life-threatening systemic illness and associated with varying immunological parameters.Aim:We conducted a study in a tertiary care center of eastern India to determine the clinical pattern, immunological profile of patients with cutaneous manifestations of systemic LE (SLE) and their relationship with organ involvement.Materials and Methods:Fifty-five consecutive patients attending dermatology OPD having features consistent with cutaneous LE and fulfilling the criteria of SLE were included. After proper history taking and clinical examination, routine blood and antinuclear antibody (ANA) profile, histopathological examination, and direct immunofluorescence test were undertaken.Results:Among 55 patients, 49 were female. ANA positivity was the most common association, followed by photosensitivity, malar rash, arthritis, oral ulcer, immunological markers, renal system involvement, discoid rash, serositis, central nervous system (CNS) involvement, and least common being the hematological involvement. Vacuolar basal cell degeneration was the commonest epidermal change and upper dermal periappendageal and perivascular lymphocytic infiltration was the commonest dermal change observed on histopathological examination. On direct immunofluorescence (DIF) granular pattern was seen in majority of patients. Statistically significant risk of kidney involvement was present both when patient had bullous lesions and DIF positivity of unexposed (DIF-UE) skin. CNS involvement was seen in five patients and it was found to be significantly associated with purpuric lesions.Conclusion:This study reveals cutaneous lesions and DIF testing could be reliable predictors of systemic involvement and strongly suggests DIF testing, routinely in all patients of SLE.

Clinicopathological Pattern of Non-lupus Full House Nephropathy.

Background and Aims:Full-house immunofluorescence in a kidney biopsy is a common observation in lupus nephritis (LN) and was previously used synonymously with the diagnosis of LN. Though a minority of the patients will develop features suggestive of SLE during follow-up, a majority of the patients will continue without any clinical or serological evidence of systemic lupus erythematosus (SLE) over time. Our aim to conduct this study was to work up the clinicopathological spectrum of these “full-house” nephropathies (FHN) which were not due to lupus nephritis.Methods:A total of 6244 renal biopsies were evaluated at SGPGIMS Lucknow from January 2007 to December 2017 for full-house immunofluorescence. All those patients who had no clinical or serological evidence of SLE at the time of renal biopsy or at any time during follow up were included.Results:Among 498 patients with full house immunofluorescence, 81 patients had no clinical or serological evidence of SLE at the time of renal biopsy or at any time during follow up. The prevalence of non-lupus FHN in this study was 19.4%, and the major diagnoses were membranous nephropathy (25.9%), IgAN (22.2%), MPGN (14.8%), DPGN (12.3%), Crescentic GN (12.3%), Amyloidosis (8.6%), C1q nephropathy (3.7%).Conclusions:Full-house nephropathy (FHN), not otherwise suggestive of lupus nephritis, can also be found in a number of other conditions. Non-lupus full house nephropathy is an umbrella term for such cases which do not satisfy the standard criteria of SLE. This will prevent misclassifying these patients into SLE and further prevent them from unnecessary immunosuppression protocols.

EULAR/ACR classification criteria for SLE

Supported by both the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) from the beginning, a large transatlantic, and in many phases worldwide, project has led to new classification criteria for systemic lupus erythematosus (SLE). The project had ambitious goals, particularly maintaining the high specificity of the ACR criteria, while reaching a sensitivity close to the Systemic Lupus International Collaborating Clinics (SLICC) 2012 criteria. The validation data suggest that the new criteria reached this goal, with a specificity of 93% (as for the ACR criteria) and a sensitivity of 96% (vs 97% for the SLICC criteria). The new EULAR/ACR classification criteria use positive antinuclear antibodies (ANA) as an entry criterion and have weighted items, ranging from 2 (for delirium, non-infectious fever and anti-phospholipid antibodies) to 10 (for class III or IV lupus nephritis). The cut-off for classification is 10, reached by class III/IV nephritis alone. Items are organized in domains, within which only the highest item is to be counted. Instead of many defined exclusions, one rule is used for all, namely that items are to be attributed to SLE and counted only if there is no more likely alternative diagnosis. These criteria are now expected to be externally validated in various other cohorts. The team spirit and collegiality characteristic for this EULAR/ACR criteria effort will hopefully facilitate future international projects on SLE.

Factors associated with damage accrual in patients with systemic lupus erythematosus with no clinical or serological disease activity: a multicentre cohort study.

Evaluating the contribution of glucocorticoid use to organ damage in systemic lupus erythematosus is confounded by glucocorticoid use in active disease. We sought to determine the independence of the contribution of glucocorticoid use to damage accrual from associations with disease activity by analysing patients without measurable disease activity. Patients (age >18 years) who met the criteria for systemic lupus erythematosus were recruited from 13 centres in Australia, Indonesia, Japan, Malaysia, the Philippines, Singapore, Taiwan, and Thailand, and followed longitudinally. Disease activity (Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K] and Physician Global Assessment [PGA] scores) and treatment details were recorded at each visit (at least once every 6 months), and organ damage measured annually according to the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Glucocorticoid use during the study period was recorded as any exposure to prednisolone, cumulative prednisolone exposure, and time-adjusted mean daily prednisolone dose. Multivariate survival analyses were used to examine time-dependent associations of glucocorticoid use with damage accrual (defined as an increase of ≥1 on SDI). A SLEDAI-2K score of 0 was taken to indicate the absence of clinical and serological disease activity; a subset of patients without disease activity during the study were defined by a time-adjusted mean SLEDAI-2K (AMS) score of 0. Between May 1, 2013, and Dec 31, 2016, 1707 patients were recruited. Over a median observation period of 2·2 years (IQR 1·5-3·0), damage accrual events were observed in 255 (14·9%) patients. 1405 (82·3%) of patients were exposed to prednisolone, with a median time-adjusted mean prednisolone dose of 5·0 mg/day (IQR 1·9-8·8). As SLEDAI-2K and PGA scores were highly correlated, two multivariable models were set, each including one of these two variables. In the model including AMS score, baseline SDI damage (SDI >0) was independently associated with damage accrual (HR 1·32 [95% CI 1·01-1·73], p=0·0427). In the other model, time-adjusted mean PGA score was independently associated with damage accrual (1·05 [1·02-1·08], p=0·0012). In both models, factors independently associated with damage accrual included time-adjusted mean prednisolone dose, age at enrolment, and ethnicity (Asian vs non-Asians). 157 (9·2%) patients had an AMS score of 0 (no disease activity), among whom 103 (65·6%) had glucocorticoid exposure and the median time-adjusted mean prednisolone dose was 2·0 mg/day (IQR 0·0-5·0). Accrual of irreversible organ damage occurred in 21 (13·4%) of these patients and was independently associated with time-adjusted mean prednisolone dose (HR 1·14 [95% CI 1·03-1·26], p=0·0117), time-adjusted mean PGA score (1·13 [1·03-1·23], p=0·0144), and age at enrolment (1·04 [1·01-1·07], p=0·0061), but not baseline SDI damage (0·94 [0·43-2·06], p=0·8675). Glucocorticoid use contributes to damage accrual in systemic lupus erythematosus independently of the presence of clinical or serological disease activity. UCB Pharma, GlaxoSmithKline, Janssen, Bristol-Myers Squibb, and AstraZeneca (to the Asia-Pacific Lupus Collaboration).

Vasculitis Retinae- A Rare Presentation of SLE

Systemic lupus erythematosus (SLE) is a rare complex autoimmune disease characterized by autoantibody formation against double strand DNA and antinuclear antibody (ANA), complement activation, and deposition of immune complexes in tissues and organs. In normal population only 0.03% suffer from SLE, among them 90% are female between the age of 20 to 30 yrs. SLE can involve any region of the visual system. Although ocular manifestations are not part of the classification criteria for SLE but retinal involvement is the most common intraocular lesion observed in up to one-third of SLE patients. The most common extra ocular lesion is keratoconjunctivitis sicca. Ocular manifestations are rarely reported at the time of disease onset, but are usually associated with active generalized systemic disease. Due to low frequency of SLE and only one third of them have ocular involvement, so reports about retinal vasculitis are very rare. But fortunately a case of Vasculitis retinae due to SLE was admitted in Anwer Khan Modern Medical College & Hospital on 04/12/2018
 Anwer Khan Modern Medical College Journal Vol. 10, No. 2: July 2019, P 179-182

Prothrombotic State, Platelet Activation and Netosis in Systemic Lupus Erythematosus

Introduction: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown origin characterized by a hypercoagulable state and a high mortality rate. Mechanisms that cause the accelerated deterioration of cardiovascular health in SLE are unknown. Objectives: to characterize the prothrombotic state in SLE patients by global coagulation assays and the contribution of platelets, endothelial damage, microparticles and neutrophil extracellular traps (NETs) in their prothombotic profile. Material and methods: 72 patients and 90 healthy controls were recruited. Patients were classified according to clinical characteristics in: 32 with lupus (SLE group), 29 with SLE and antiphospholipid antibodies (aFL, SLE+aFL group) and 12 who met the criteria for SLE and antiphospholipid syndrome (APS, SLE+APS group). Experimental protocol was approved by La Paz University Hospital Ethics Committee. Venous blood collected in BD sodium citrate tubes (3.2%) was centrifuged at 150 g for 20 min at 23ºC to obtain platelet-rich plasma (PRP). PPP was obtained by centrifugation at 1500 g for 15 min at 23ºC. To obtain neutrophils, whole blood was centrifuged to 1600 rpm 25 min using a Ficoll gradient and red cells were lysed. Rotational thromboelastometry (ROTEM®) was performed in naTEM condition. Clotting time (CT, time from start of measurement until initiation of clotting [in seconds]); alpha angle (tangent to the curve at 2-mm amplitude [in degrees]), Ax (clot firmness at time x, [in mm]) and maximum clot firmness (MCF, [in mm]) were recorded. Procoagulant activity associated to microparticle's content of tissue factor was determined in PPP by Calibrated Automated Thrombogram (CAT) using MP-reagent (4 mM phospholipids, Diagnostica Stago, Spain). We evaluated the endogenous thrombin potential (ETP, the total amount of thrombin generated over time); the lag time (the time to the beginning of the explosive burst of thrombin generation); the peak height of the curve (the maximum thrombin concentration produced) and the time to the peak. Thrombin generation associated to NETs was also measured by CAT. Neutrophils from healthy controls or from LES patients were stimulated with 100 nM PMA in RPMI medium during 45 min at 37º and then cocultivated with PRP adjusted to 105 platelets/µL. NETs formation was verified by fluorescent microscopy performed with DAPI and an anti-myeloperoxidase antibody. Plasma levels of LDL-ox, E-Selectin and PAI-1 were determined by Elisa (R&D Systems, MN, USA and Affymetrix eBioscience, Vienna, Austria, respectively). Platelet activation was analysed by flow cytometry (FCM, FACScan, BD Biosciences). Fibrinogen receptor activation was evaluated through PAC1-FITC binding and release of granule's content was assessed with monoclonal antibodies (mAbs) anti-CD63 and anti P-selectin in quiescent and 100 µM TRAP and 10 µM ADP stimulated platelets. Data were analysed with Graphpad prism and p ≤0.05 was stablished as statistical significance. Results: PAI-1 plasma level was increased in all patient's groups, whereas LDL-ox and E-selectin showed no differences with control cohort (Fig.1). ROTEM demonstrated a procoagulant profile in SLE and SLE+aPL but not in SLE+APS group (Fig. 2). PAI-1 levels correlated with several ROTEM parameters (Table 1). SLE patients and SLE+aFL showed a basal platelet activation. Moreover, SLE group exposed more P-selectin and CD63 than controls (Fig.3). Regarding thrombin generation associated to tissue-factor content of microparticles, no differences were observed between SLE patients and healthy controls. On the other hand, SLE patients had an increased peak of thrombin generation related to NETs formation (control group: 170.3± 58.0, SLE patients: 230.6±39.3, p=0.019). Conclusions: ROTEM® detected a hypercoagulable state in SLE and SLE+aPL patients. The hypercoagulable state might be linked to increased PAI-1 plasma levels and basal platelet activation in SLE and SLE+aPL groups. Moreover, neutrophils from SLE patients seemed to present a basal activation that induced a NETs-related procoagulant state in these patients. SLE+APS patients did not show a hypercoagulable state perhaps because of the presence of lupus anticoagulant and/or to therapeutic treatment of these patients. This work was supported by grants from the FIS-FONDOS FEDER (PI15/01457, NB). NVB holds a Miguel Servet tenure track grant from FIS-FONDOS FEDER (CP14/00024). Disclosures Fernandez-Bello: Novartis, Pfizer, ROCHE, Stago: Speakers Bureau. Robles:ABBVIE, SANDOZ FARMACEUTICA: Speakers Bureau. Álvarez Roman:Sobi: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Takeda: Research Funding; NovoNordisk: Consultancy, Speakers Bureau. Canales:Celgene: Honoraria; Gilead: Honoraria; Novartis: Honoraria; Janssen: Honoraria, Speakers Bureau; Sandoz: Honoraria; iQone: Honoraria; Takeda: Speakers Bureau; SOBI: Research Funding; Karyopharm: Honoraria; F. Hoffmann-La Roche Ltd: Honoraria, Speakers Bureau. Jimenez-Yuste:Bayer, CSL Behring, Grifols, Novo Nordisk, Octapharma, Pfizer, Roche, Sobi, Shire: Consultancy, Honoraria, Other: reimbursement for attending symposia/congresses , Research Funding, Speakers Bureau. Butta:Novartis: Consultancy; Roche, Pfizer: Speakers Bureau.

Spinal cord syndromes in patients with systemic lupus erythematosus: differentiating lupus myelitis, neuromyelitis optica, and multiple sclerosis.

Non-infectious myelitis in systemic lupus erythematosus (SLE) may be due to SLE myelitis, comorbid multiple sclerosis (MS), or neuromyelitis optica (NMO). We compared characteristics of these three conditions in SLE patients at a large academic institution. We searched for neurologic diagnoses of SLE myelitis, NMO myelitis, and MS myelitis among 2297 patients with at least four 1997 American College of Rheumatology revised criteria for SLE between 2000 and 2015. Each subject was reviewed by a neurologist to confirm the underlying neurologic diagnosis. Demographic, clinical, laboratory, and radiographic data were extracted and compared using Fisher's exact test, analysis of variance, and Wilcoxon rank-sum test. Fifteen of the 2297 subjects with SLE (0.7%) met criteria for a spinal cord syndrome: seven had SLE myelitis, three had AQP4 seropositive NMO, and five had MS. The median SLE Disease Activity Index 2000 score at time of neurologic syndrome presentation was higher in SLE myelitis subjects (8, interquartile range (IQR) 7-16) compared with subjects with NMO (6, IQR 0-14) or MS (2, IQR 0-4), p = 0.02. Subjects with SLE myelitis were also more likely to have elevated anti-dsDNA antibodies at presentation (86%) compared with subjects with NMO (33%) or MS (0%), p = 0.03. Myelitis occurs rarely among patients with SLE. Compared with subjects with SLE + NMO and subjects with SLE + MS, subjects with SLE myelitis had higher SLE disease activity at presentation.

Salivary dysbiosis and the clinical spectrum in anti-Ro positive mothers of children with neonatal lupus

Mothers giving birth to children with manifestations of neonatal lupus (NL) represent a unique population at risk for the development of clinically evident pathologic autoimmunity since many are asymptomatic and only become aware of anti-SSA/Ro positivity (anti-Ro+) based on heart block in their fetus. Accordingly, we hypothesized that the microbiome in saliva is associated with the development of autoreactivity and in some cases the progression in health status from benign to overt clinical disease including Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE). The study comprised a clinical spectrum of anti-Ro+ mothers, all of whom gave birth to a child with NL: 9 were asymptomatic or had an undifferentiated autoimmune disease (Asym/UAS) and 16 fulfilled criteria for SS and/or SLE. Microbial diversity was reduced across all levels from kingdom to species for the anti-Ro+ mothers vs healthy controls; however, there were no significant differences between Asym/UAS and SS/SLE mothers. Relative abundance of Proteobacteria and more specifically class Betaproteobacteria decreased with clinical severity (healthy controls < Asym/UAS < SS/SLE). These ordered differences were maintained through the taxonomic hierarchy to three genera (Lautropia, Comamonas, and Neisseria) and species within these genera (L. mirabilis, N. flavescens and N. oralis). Biometric analysis comparing von Willebrand Factor domains present in human Ro60 with L. mirabilis proteins support the hypothesis of molecular mimicry. These data position the microbiome in the development of anti-Ro reactivity and subsequent clinical spectrum of disease.

Cutaneous Lupus Erythematosus Patients With a Negative Antinuclear Antibody Meeting the American College of Rheumatology and/or Systemic Lupus International Collaborating Clinics Criteria for Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a disorder that is heterogeneous and can be difficult to diagnose. One hallmark of the disease is the presence of antinuclear antibodies (ANAs), a feature that has been incorporated into multiple classification criteria over the years. In this study, we used a database of patients with cutaneous lupus erythematosus (CLE) to determine how many had a negative ANA and met criteria for SLE using the American College of Rheumatology (ACR) and/or Systemic Lupus International Collaborating Clinics (SLICC) criteria. We used a database of 301 biopsy-proven CLE patients that contained information including ANA status and the presence of features of SLE. The database was searched for patients who had a negative ANA result and whether or not they met SLE criteria using the ACR and/or SLICC criteria. Of the 301 patients with biopsy-proven CLE and a known ANA, 111 had a negative ANA test (36.9%) and 27 had an ANA test that fluctuated (33.3%). In all, 20 ANA-negative patients met SLE criteria (18.0%), and 12 patients with a fluctuating ANA test met SLE criteria (44.4%). Of all patients who had either a negative or fluctuating ANA result and who met criteria for SLE (n = 32), 27 patients had involvement of ≥1 organ system other than skin (84.4%), and 13 patients had involvement of ≥2 organ systems other than skin (40.6%). Our results show that an ANA is not always present in patients with systemic disease. This fact should be taken into consideration when devising SLE classification criteria to be used for clinical trials.

Prednisolone dose during treatment of tuberculosis might be a risk factor for mortality in patients with systemic lupus erythematosus: a hospital-based cohort study.

Patients with systemic lupus erythematosus (SLE) are at high risk of tuberculosis (TB) because of their immunocompromised status and the use of immunosuppressive drugs. In endemic regions, TB complicates the diagnosis and treatment of SLE, but the risk factors of mortality in these patients have not been investigated. In this study, we reviewed medical records during 2006-2016. Patients who fulfilled the 1997 American College of Rheumatology SLE criteria and presented with definite TB were enrolled. The primary outcome was mortality during TB treatment. There were 5388 SLE patients screened, and 30 patients were enrolled. Seven patients died during follow-up. Compared with the survival group, patients in the mortality group had significantly more central nervous system involvement of TB, higher Systemic Lupus Erythematosus Disease Activity Index-2000 scores and more cyclophosphamide use before TB, and higher prednisolone dose before and during TB treatment. Cox regression showed that prednisolone dose during TB treatment was an independent risk factor for mortality (per 10 mg/day increase, hazard ratio (HR) 1.61, p = .019). For SLE patients, prednisolone dose during TB treatment is an independent risk factor for mortality. Keeping prednisolone dose at less than 25 mg per day during TB treatment might be a reasonable strategy in these patients.

Dermoscopy in the differential diagnosis between malar rash of systemic lupus erythematosus and erythematotelangiectatic rosacea: an observational study.

Malar rash is one of the three cutaneous diagnostic criteria of systemic lupus erythematosus (SLE). Although its clinical recognition is often straightforward, the differential diagnosis with erythematotelangiectatic rosacea may sometimes be challenging. To describe dermoscopic features of SLE malar rash and investigate the accuracy of dermoscopy for the differential diagnosis with erythematotelangiectatic rosacea. A representative dermoscopic image of target areas was evaluated for the presence of specific features. Fisher's test was used to compare their prevalence between the two cohorts, and accuracy parameters (specificity, sensitivity, and positive and negative predictive values) were evaluated. Twenty-eight patients were included in the analysis, of which 13 had SLE malar rash and 15 erythematotelangiectatic rosacea. The main dermoscopic features of malar rash were reddish/salmon-coloured follicular dots surrounded by white halos ('inverse strawberry' pattern), being present in 53.9% of the cases, while network-like vessels (vascular polygons) turned out to be the main feature of erythematotelangiectatic rosacea, with a prevalence of 93.3%. The comparative analysis showed that the 'inverse strawberry' pattern was significantly more common in SLE malar rash, with a specificity of 86.7%, while vascular polygons were significantly more frequent in rosacea, with a specificity of 92.3%. Dermoscopy may be a useful support to distinguish SLE malar rash and erythematotelangiectatic rosacea by showing peculiar features.

P4440Assessment of left atrial function in patients with systemic lupus erythematosus with and without neuropsychiatric manifestations: association with cardiovascular events

Abstract Introduction Cardiac involvement in Systemic Lupus Erythematosus (SLE) may lead to left ventricular (LV) hypertrophy with possible impairment of LV diastolic function and left atrial (LA) function, particularly in patients with severe forms of SLE with neuropsychiatric manifestations (NPSLE) and can also be associated with cardiovascular outcome. Purpose We evaluated the prevalence of LV diastolic dysfunction and LA dysfunction in a large cohort of SLE patients including also NPSLE patients, and their association with the occurrence of cardiovascular events (cerebrovascular accidents, lung-embolism, coronary revascularisation, heart failure hospitalisations and development of supraventricular arrhythmias). Methods A total of 102 SLE patients (87% female, 42±15 years) were included, of which 43 (42%) with NPSLE according to a multidisciplinary team assessment. All patients fulfilled the American College of Rheumatology (ACR 1997) and Systemic Lupus Erythematosus International Collaborating Clinics (SLICC 2012) classification criteria for SLE. Echocardiography was performed at the first visit: LV diastolic function was assessed according to current recommendations and including Tissue Doppler Imaging measures; LA volume (LAVI) was also measured and LA function was assessed by LA reservoir strain using 2D speckle tracking imaging. Results In the SLE patients, mean LV mass index was 82±32 g/m2, 29% of patients showed an e'septal &lt;10, 7% an E/e'&gt;14, 16% a LAVI&gt;34 ml/m2 and 5% a tricuspid velocity &gt;2.8m/s. When applying the currently recommended multiparametric approach, only 4% of SLE patients showed LV diastolic dysfunction. In NPSLE patients, the prevalence of LV diastolic dysfunction was not significantly higher (5%). However, an impaired LA reservoir strain (based on the median value of 25%) was observed in 54% of the total SLE population and in 77% of NPSLE patients suggesting higher sensitivity of this parameter to detect impaired LA function and LV diastolic function. During a median follow up of 11 years (Interquartile range: 4–19 years), 43 (42%) patients developed a cardiovascular event. Kaplan-Meier curve analysis showed that SLE patients with impaired LA strain &lt;25% experienced higher cumulative rates of cardiovascular events, as compared to SLE patients with LA strain≥25% (Chi-square 4.350; Log rank p=0.037). At the uni- and multivariate Cox-regression models, LA strain showed significant association with cardiovascular events (hazard ratio [HR]:0.944; 95% confidence interval [CI]: 0.893–0.997; p=0.039) together with age (HR: 1.030; 95% CI: 1.002–1.059; p=0.039) after correcting for LV mass index and LV diastolic dysfunction. LA reservoir strain Conclusions LA dysfunction as assessed by LA reservoir strain is significantly impaired in SLE and particularly in NPSLE patients and improve detection of myocardial involvement in these patients. Furthermore, LA reservoir strain is independently associated with the development of cardiovascular events.

P607Myocardial injury in systemic lupus erythematosus defined by cardiac magnetic resonance imaging: clinical and echocardiographic characteristics

Abstract Background Lupus myocarditis (LM) occurs in 5–10% of patients with systemic lupus erythematosus (SLE). Subclinical myocardial inflammation is detected in 37% at post mortem. Echocardiographic strain analyses (speckle tracking [STE]) supports subclinical myocardial dysfunction in SLE. Tissue characterization by cardiac magnetic resonance (CMR) identifies myocardial inflammation, necrosis/fibrosis, detecting clinical and subclinical myocardial injury (MIN). It is the non-invasive diagnostic modality of choice for myocarditis (all types) based on the Lake Louise criteria (LLC). The utility of CMR is limited by cost (in resource limited settings) as well as intolerance of / contra-indications to CMR. Purpose Determine prevalence of MIN in SLE (as per LLC). Compare clinical and echocardiographic features of patients with and without MIN. Identify echocardiographic predictors of MIN. Methods A prospective crossectional study was done at Tygerberg Hospital, Western Cape, South Africa. Adult inpatients, fulfilling the 2012 classification criteria for SLE were screened for inclusion. Echocardiography (echo) included strain analyses (segmental and global [GLS]) through STE and regional function assessment (wall motion score (WMS)). Patients were grouped according to CMR evidence of MIN (absent LLC [AC]; single criterion [SC]; fulfilling LLC). Clinical, laboratory and echo parameters were compared between groups. Logistic regression and ROC were used to determine predictors of MIN. Results 49/106 SLE patients screened were included (Figure 1). The median age was 27 years (IQR: 22–35) and 88% were female. 46.9% of patients had MIN (≥1 criterion): 12.2% fulfilled LLC and 34.7% had a SC. Demographic features, cardiac risk factors (including antiphospholipid syndrome) and renal disease were similar among groups. Compared to the AC group, SLE disease activity was higher in patients fulfilling LLC (p=0.022), but not in the SC group (p=0.813). A clinical and echo diagnosis of LM was made in all patients fulfilling LLC (p&lt;0.001), in 17.6% of patients in the SC group (p=0.026) vs none in the AC group. Anti-DsDNA (p=0.054) and anti-B2GP1 (p=0.081) were more frequently positive in the SC vs AC group. The WMS was higher in LLC and SC groups (p=0.006; p=0.083) with mid and basal strain more impaired in patients with MIN (p=0.043; p=0.047). LVID and mid STE score (number of segments with impaired STE) combined was the best predictor of MIN (OR: 2.1; 95% CI: 1.2–3.5; p=0.008). The predictive model had an AUC of 0.791 (PPV: 81.8%; NPV: 86.4%). Figure 1 Conclusion CMR is limited by a high exclusion rate in SLE, mainly due to renal disease. CMR evidence of MIN is common in SLE, even in the absence of clinical myocardial dysfunction or high lupus activity. Impaired echo regional and global function occurs more frequently in patients with MIN. STE combined with LVID predicts the presence of MIN detected by CMR and has potential as a cost effective screening tool.

Evaluation of remission definitions for systemic lupus erythematosus: a prospective cohort study.

Validated outcome measures are needed from which to derive treatment strategies for systemic lupus erythematosus (SLE). However, no definition of remission for SLE has been widely adopted. The Definitions of Remission in Systemic Lupus Erythematosus (DORIS) group has proposed a framework with multiple potential definitions of remission. In this study, we aimed to assess the attainability and effect on disease outcomes of the DORIS definitions of remission, compared with the lupus low disease activity state (LLDAS), in patients with SLE. In this prospective cohort study, we enrolled patients with SLE from 13 international centres that are part of the Asia Pacific Lupus Collaboration. Eligible patients were older than 18 years and fulfilled one of two classification criteria for SLE (1997 American College of Rheumatology criteria or the 2012 Systemic Lupus International Collaborating Clinics criteria). Visits were according to clinical need, with a minimum frequency of one visit per 6 months. We assessed attainment of remission on the basis of the eight DORIS definitions of remission, which varied in terms of serological activity, glucocorticoid use, and use of immunosuppresive agents; attainment of LLDAS; and disease flares at each visit. Irreversible organ damage accrual was recorded annually. Our primary aim was to assess exposure of patients to each of the remission definitions or LLDAS, and the respective association of these states with accrual of irreversible organ damage as the primary outcome measure. Occurrence of disease flares was the key secondary outcome. We used time-dependent Cox proportional hazards models and generalised linear models to assess DORIS definitions of remission and LLDAS in terms of their association with damage accrual and disease flares. Between May 1, 2013, and Dec 31, 2016, 1707 patients with SLE were recruited and followed for a mean of 2·2 years (SD 0·9), totalling 12 689 visits. Remission, depending on DORIS definition, was achieved in 581 (4·6%) to 4546 (35·8%) of 12 689 visits. Spending 50% or more of observed time in any remission state was associated with a significant reduction in damage accrual, except for the two most stringent remission definitions, for which the frequency of attainment was lowest. Remission definitions disallowing serological activity were associated with the greatest reductions in disease flares. LLDAS was more attainable than any remission definition and was associated with a similar magnitude of protection from damage accrual and disease flares. Sustained remission and LLDAS were associated with a wider spread of effect sizes for reduction in risk of damage. By analysing patients who met the definition for LLDAS but not remission, we found that LLDAS was significantly associated with reduction in damage accrual, independent of all definitions of remission, except the least stringent. Attainment of remission was associated with significant reductions in damage accrual and disease flares. LLDAS was more achievable than remission based on the DORIS criteria, but was similarly protective. Remission definitions with less stringency might be insufficiently distinct from LLDAS to substantially affect outcome measures, and further studies are needed to distinguish the protective effects of the various remission definitions. UCB, GlaxoSmithKline, Janssen, Bristol-Myers Squibb, and AstraZeneca.

Risk factors for progression of carotid intima-media thickness in patients with systemic lupus erythematosus: protocol for an observational cohort study in China

IntroductionAccelerated atherosclerosis is a major complication of systemic lupus erythematosus (SLE), and it leads to increased cardiovascular morbidity and mortality in patients with SLE. This study aimed to investigate the...