Systemic Lupus Erythematosus Arthritis Research Articles

Arthritis in Systemic Lupus Erythematosus: From 2022 International GISEA/OEG Symposium.

Musculoskeletal involvement is one of the most common manifestations of systemic lupus erythematosus (SLE), with a negative impact on both quality of life and overall prognosis. SLE arthritis can be classified into three different subtypes, with different prevalence and characteristic biomarkers and MRI findings. Identifying the pathogenetic mechanisms underlying musculoskeletal manifestations’ development is crucial to develop therapeutic strategies to suppress synovial inflammation, prevent erosions and deformities, and improve SLE patients’ quality of life. Hence, here we discuss the main pathogenetic mechanisms and therapeutic approaches of musculoskeletal manifestations of SLE from the 2022 International GISEA/OEG Symposium.

Performance analysis of Luminex and ELISA to profile serum IP-10 as a biomarker in systemic lupus erythematosus.

Interferon-γ inducible protein-10 (IP-10) is a promising biomarker in systemic lupus erythematosus (SLE). The optimal quantification platform has not yet been identified. We compared the performance of bead-based multiplex assay (Luminex) and high-sensitivity enzyme-linked immunosorbent assay (hs-ELISA) for profiling serum IP-10 as a biomarker of lupus activity. A cross-sectional study was conducted on outpatients with SLE. Serum IP-10 was measured simultaneously on Luminex and hs-ELISA, and correlation between platforms was assessed. Additionally, IP-10 levels were tested against disease activity and organ involvement. One-hundred and forty-one patients (88% women; 38 years old) were studied. Median IP-10 levels were 100.9 (125.2) pg/mL by Luminex and 156.5 (191.7) pg/mL by hs-ELISA. Correlation analysis showed Spearman's ρ = 0.621 (p < 0.0001) between Luminex and hs-ELISA. Quantification of IP-10 by Luminex showed a significant correlation (ρ = 0.198; p = 0.021) with disease activity, while this was not observed (ρ = 0.036; p = 0.683) when measured using hs-ELISA. Serum IP-10 levels were lower in quiescent patients than in those with active disease (70.8 [68.4] versus 114.3 [123.9] pg/mL; p = 0.024), with an AUC-ROC = 0.62 (p = 0.029), sensitivity = 47.9%, specificity = 77.5%, and positive likelihood ratio = 2.1. Patients with active arthritis had higher IP-10 levels than non-arthritis patients (158.1 [505.4] versus 94.1 [114.0] pg/mL; p = 0.008), with an AUC-ROC = 0.73 (p = 0.0009), sensitivity = 72.7%, specificity = 66.4%, and positive likelihood ratio = 2.1. No other type of organ involvement was identified by serum IP-10. Luminex performs better than hs-ELISA as a quantification platform for IP-10 as it correlates with disease activity and identifies active arthritis in SLE.

Porphyromonas gingivalis amount in the tongue biofilm is associated with erosive arthritis in systemic lupus erythematosus.

Several data have demonstrated the occurrence of erosive arthritis in Systemic Lupus Erythematosus (SLE) patients. However, a few studies have focused on the pathogenic mechanisms involved in this feature. The implication of oral pathogens has been proved in Rheumatoid Arthritis: in particular, Porphyromonas gingivalis (Pg), by inducing citrullination, could trigger autoimmune response. Here, we evaluated amount of Pg on the tongue in a cohort of SLE patients with arthritis, focusing on the association with the erosive phenotype. SLE patients with arthritis were enrolled. DAS28 was applied to assess activity. Erosive damage was evaluated by ultrasound at level of MCP (metacarpophalangeal) and PIP (proximal interphalangeals) joints. All subjects underwent a tongue cytologic swab in order to quantify the amount of Pg (real-time PCR). The bacterium expression was obtained from the ratio between the patient's DNA amount and that obtained from healthy subjects. 33 patients were enrolled (M/F 3/30; median age 47years, IQR 17; median disease duration 216 months, IQR 180): 12 of them (36.4%) showed erosive damage, significantly associated with ACPA positivity (p = 0.03) and higher values of DAS28 (p = 0.01). A mean ratio of 19.7 ± 31.1 was found for Pg amount. Therefore, we used Pg mean values as threshold, identifying two groups of patients, namely, highPg and lowPg. Erosive damage was significantly more frequent in highPg patients in comparison with lowPg (60.0% vs 26.0%, p = 0.001). Furthermore, highPg patients showed higher prevalence of skin manifestations, serositis, and neurological involvement (p = 0.005, p = 0.03, p = 0.0001, respectively). The possible contribution of oral microbiota in SLE erosive arthritis was here evaluated for the first time, finding a significant association between erosive damage and higher expression of Pg at tongue level.

Erosive arthritis in systemic lupus erythematosus: application of cluster analysis.

In the present study, we applied cluster analysis (CA) in SLE patients with joint involvement to identify which disease subset most commonly develops erosive damage. We collected clinical and laboratory data of SLE patients with a clinical history of joint involvement (arthritis/arthralgia). Ultrasonographic assessment was performed at level of MCPs and PIPs joints, to identify erosive arthritis, defined as the presence of erosions in at least one joint. Moreover, we detected RF, ACPA anti-CarP, and Dkk1 serum levels. We applied an unsupervised hierarchical CA to identify the aggregation of patients into different subgroups sharing common characteristics in terms of clinical and laboratory phenotypes. CA included 112 SLE patients (M/F 6/106; median age 45 years, IQR 17; median disease duration 96 months, IQR 165). Arthritis was observed in 82 patients (73.2%) and inflammatory arthralgia in 30 (26.8%). US-detected erosive arthritis was observed in 29 patients (25.9%). CA on clinical and laboratory features allowed the identification of four main clusters: in particular erosive arthritis was located in a cluster including renal and neuropsychiatric involvement, serositis, positivity for ACPA, anti-Carp, anti-Sm, anti-RNP, detectable levels of Dkk1. The application of CA made it possible to better characterise SLE phenotype including erosive arthritis. In particular, feature-driven CA leads to the identification of a more aggressive disease, due to a common pathogenic mechanism.

Erosive arthritis in systemic lupus erythematosus: not only Rhupus.

Systemic lupus erythematosus (SLE)-related arthritis has been traditionally defined as non-erosive and is therefore considered a minor manifestation requiring a mild treatment. However, the concept of non-erosive arthritis in SLE has been challenged with the advent of sensitive imaging techniques, such as high-resolution ultrasound with power Doppler or magnetic resonance. The application of these new imaging tools has demonstrated that up to 40% of SLE patients with joint involvement can develop erosive damage. Thus, this more aggressive phenotype can be identified not only in patients overlapping with rheumatoid arthritis (RA). This issue has been considered for the first time in the classification criteria proposed by Systemic Lupus International Collaborating Clinics in 2012, in which the old definition of "non-erosive arthritis" was replaced with either synovitis or tenderness in two or more joints with morning stiffness, suggesting the possible presence of an erosive phenotype. Accordingly, the 2019 EULAR/ACR's SLE recommendations advise treatment with immunosuppressant or biological drugs for patients with RA-like moderate arthritis. As a result, several studies have investigated the presence of biomarkers associated with SLE erosive damage. A relevant role seems to be played by the autoantibodies directed against post-translational modified proteins: above all, a significant association has been observed with antibodies directed against citrullinated and carbamylated proteins. Conversely, the rheumatoid factor was not associated with this more aggressive SLE-related arthritis. Nonetheless, some pro-inflammatory factors have been associated with erosive damage in SLE patients. These results suggest new pathogenic mechanisms underlining erosive arthritis, only partially shared with RA. Hence, in the present narrative review, we summarized available data about erosive arthritis in SLE patients, in the light of its impact on therapeutic decisions.

Arthritis in systemic lupus erythematosus is characterized by local IL-17A and IL-6 expression in synovial fluid.

SummaryArthritis is a common clinical feature of systemic lupus erythematosus (SLE) and is usually non‐erosive, as opposed to rheumatoid arthritis (RA). While RA synovial pathology has been extensively studied, little is known about the pathophysiology of lupus arthritis. Here, we aimed to explore the cytokine and cellular compartments in synovial fluids of SLE patients with arthritic manifestations. Acellular synovial fluid and paired serum samples from SLE patients (n = 17) were analyzed with cytokine bead array for T helper‐associated cytokines. From two SLE patients, synovial fluid mononuclear cells (SFMC) could also be captured and were analyzed by multiparameter flow cytometry to dissect T cell, B cell, monocyte and dendritic cell phenotypes. SLE‐derived SFMC were further stimulated in vitro to measure their capacity for producing interferon (IFN)‐γ and interleukin (IL)‐17A. All patients fulfilled the ACR 1982 classification criteria for SLE. Clinical records were reviewed to exclude the presence of co‐morbidities such as osteoarthritis or overlap with RA. IL‐17A and IL‐6 levels were high in SLE synovial fluid. A clear subset of the synovial CD4+ T cells expressed CCR6+, a marker associated with T helper type 17 (Th17) cells. IL‐17A‐production was validated among CD4+CCR6+ T cells following in‐vitro stimulation. Furthermore, a strong IFN‐γ production was observed in both CD4+ and CD8+ cells. Our study shows high IL‐17A and IL‐6 levels in synovial fluids of patients with lupus arthritis. The Th17 pathway has been implicated in several aspects of SLE disease pathogenesis and our data also point to Th17 involvement for lupus arthritis.

Measuring inflammatory arthritis in patients with systemic lupus erythematosus using clinical disease activity index

Background: Inflammatory polyarthritis is seen in ~80% of patients with systemic lupus erythematosus (SLE); yet, there is no validated “instrument” for its assessment. The commonly used measures of disease activity, namely SLE Disease Activity Index 2000 (SLEDAI2K) and British Isles Lupus Assessment Group are complex and impractical for routine use in busy outpatient clinics. This “proof of concept” study's primary aim was to test clinical disease activity index (CDAI) as a possible instrument for measuring the joint disease in SLE that may have a face value and sensitivity to change. The secondary aim was to determine the efficacy of low-dose methotrexate in the SLE joint disease.Materials and Methods: This open-label study included the Systemic Lupus International Collaborating Clinics criteria classifiable thirty patients with SLE with inflammatory polyarthritis as the main manifestation. SLE disease activity and the joint disease activity were assessed using SLEDAI2K and CDAI, respectively, at the baseline and in the follow-up. The CDAI and the SLEDAI2K scores were compared between the first and the last visit, as well as compared with each other, using a nonparametric test (Wilcoxon signed-rank test).Results: CDAI scores improved significantly on treatment from a mean of 19.30 to 1.58 and in SLEDAI2K from 7.83 to 0.6, respectively; the pre- and the postintervention scores were statistically highly significant (P < 0.001) for both the CDAI and the SLEDAI2K. The degree of improvement as shown by SLEDAI2K change in scores and CDAI was statistically insignificant (P > 0.05), indicating similarity in their sensitivity to change. A significant number of patients achieved low disease activity status or remission in their joint disease.Conclusion: CDAI appears to be sensitive to change with treatment. Therefore, it could be used as a tool for assessing inflammatory arthritis in SLE.

Autoantibody IgG Protects Bone Erosion and Destruction in SLE Arthritis

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by high levels of autoantibodies and multiorgan tissue damage [1]. Arthritis is common in patients with SLE [2]. Bone erosion is a remarkable feature in arthritis such as rheumatoid arthritis (RA), but they are usually absent in arthritis of SLE [3]. Thus, this is particularly striking for clinical doctors because synovial biopsies from SLE patients show similar synovial inflammation to those in RA [4].

Biomarkers of erosive arthritis in systemic lupus erythematosus: Application of machine learning models.

ObjectiveLimited evidences are available on biomarkers to recognize Systemic Lupus erythematosus (SLE) patients at risk to develop erosive arthritis. Anti-citrullinated peptide antibodies (ACPA) have been widely investigated and identified in up to 50% of X-ray detected erosive arthritis; conversely, few studies evaluated anti-carbamylated proteins antibodies (anti-CarP). Here, we considered the application of machine learning models to identify relevant factors in the development of ultrasonography (US)-detected erosive damage in a large cohort of SLE patients with joint involvement.MethodsWe enrolled consecutive SLE patients with arthritis/arthralgia. All patients underwent joint (DAS28, STR) and laboratory assessment (detection of ACPA, anti-CarP, Rheumatoid Factor, SLE-related antibodies). The bone surfaces of metacarpophalangeal and proximal interphalangeal joints were assessed by US: the presence of erosions was registered with a dichotomous value (0/1), obtaining a total score (0–20). Concerning machine learning techniques, we applied and compared Logistic Regression and Decision Trees in conjunction with the feature selection Forward Wrapper method.ResultsWe enrolled 120 SLE patients [M/F 8/112, median age 47.0 years (IQR 15.0); median disease duration 120.0 months (IQR 156.0)], 73.3% of them referring at least one episode of arthritis. Erosive damage was identified in 25.8% of patients (mean±SD 0.7±1.6), all of them with clinically evident arthritis. We applied Logistic Regression in conjunction with the Forward Wrapper method, obtaining an AUC value of 0.806±0.02. As a result of the learning procedure, we evaluated the relevance of the different factors: this value was higher than 35% for ACPA and anti-CarP.ConclusionThe application of Machine Learning Models allowed to identify factors associated with US-detected erosive bone damage in a large SLE cohort and their relevance in determining this phenotype. Although the scope of this study is limited by the small sample size and its cross-sectional nature, the results suggest the relevance of ACPA and anti-CarP antibodies in the development of erosive damage as also pointed out in other studies.

Anti-carbamylated protein antibodies as a new biomarker of erosive joint damage in systemic lupus erythematosus

BackgroundThe application of more sensitive imaging techniques, such as ultrasonography (US), changed the concept of non-erosive arthritis in systemic lupus erythematosus (SLE), underlining the need for biomarkers to identify patients developing the erosive phenotype. Anti-citrullinated peptide antibodies (ACPA), associated with erosions in inflammatory arthritis, have been identified in about 50% of patients with SLE with erosive arthritis. More recently, anti-carbamylated proteins antibodies (anti-CarP) have been associated with erosive damage in rheumatoid arthritis. We aimed to assess the association between anti-CarP and erosive damage in a large SLE cohort with joint involvement.MethodsWe evaluated 152 patients (male/female patients 11/141; median age 46 years, IQR 16; median disease duration 108 months, IQR 168). All patients underwent blood draw to detect rheumatoid factor (RF) and ACPA (commercial enzyme-linked immunosorbent assay (ELISA) kit), and anti-CarP (“home-made” ELISA, cutoff 340 aU/mL). The bone surfaces of the metacarpophalangeal and proximal interphalangeal joints were assessed by US: the presence of erosions was registered as a dichotomous value (0/1), obtaining a total score (0–20).ResultsThe prevalence of anti-CarP was 28.3%, similar to RF (27.6%) and significantly higher than ACPA (11.2%, p = 0.003). Erosive arthritis was identified in 25.6% of patients: this phenotype was significantly associated with anti-CarP (p = 0.004). Significant correlation between anti-CarP titer and US erosive score was observed (r = 0.2, p = 0.01).ConclusionsSignificant association was identified between anti-CarP and erosive damage in SLE-related arthritis, in terms of frequency and severity, suggesting that these antibodies can represent a biomarker of severity in patients with SLE with joint involvement.

Musculoskeletal manifestations as determinants of quality of life impairment in patients with systemic lupus erythematosus.

Objective The objective of this study was to identify determinants of health-related quality of life (HRQoL) impairment in patients with systemic lupus erythematosus (SLE). Methods Overall, 101 SLE patients were recruited; 37 healthy subjects and 35 rheumatoid arthritis (RA) patients served as controls. HRQoL was evaluated using three patient reported outcomes (PROs): the Short Form-36 version 2 (SF-36v2) health survey, the fatigue scale version 4 (FACITv4) and the Heath Assessment Questionnaire (HAQ). A large set of demographic and clinical variables, including SLE arthritis subtypes, was evaluated searching for factors independently associated with worse QoL. Multivariate models were applied to identify factors independently associated with outcomes. Bonferroni's corrected p values < 0.05 were considered significant. Results SLE patients showed worse results than healthy controls ( p < 0.01) in all SF-36v2 domains and, with reference to the mental QoL, also than RA patients ( p < 0.01). Jaccoud's deformities, active arthritis, and fibromyalgia were the only factors independently associated with worse results in both physical and mental components summary of the SF-36v2 ( p < 0.01) and FACITv4 fatigue scale ( p < 0.01). Fragility fractures, deformities, and active arthritis negatively affected disability perception measured by the HAQ ( p < 0.01). No statistically significant differences in perceived HRQoL were highlighted between patients with deforming and erosive arthritis. However, they had significantly worse results than patients with non-deforming non-erosive arthritis across all investigated PROs ( p < 0.01). Conclusion In order to limit musculoskeletal manifestations as a source of impaired QoL in SLE patients, therapeutic strategies targeted to successfully manage active arthritis and fibromyalgia and to prevent deforming damage are needed.

Role of anti-CCP in arthritis in patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease with multi-organ involvement. Patients with SLE feature a lower tendency to develop erosive arthritis in comparison with rheumatoid arthritis (RA); however, in some arthritis cases it may be difficult to differentiate SLE from RA. Anti-cyclic citrullinated peptide (Anti-CCP) antibodies are highly-specific for RA. The current study evaluated the relationship between anti-CCP and arthritis in SLE patients. In this study, anti-CCP antibodies were tested in 300 patients with SLE. The INOVA Diagnostics QUANTA Lite™ CCP IgG ELISA and the Axis-Shield Diagnostics Diastat™ anti-CCP ELISA test were applied. Patients were divided into two groups: those with and those without arthritis. Patients with chronic arthritis (>6 weeks) had radiography done on the involved joints. Chi square and Fisher’s exact tests were applied to compare the two subsets. Anti-CCP antibodies were detected in 4.7% of all patients (CI: 2.6-7.8). Anti-CCP was positive in 6.4% of patients with arthritis and 2.3% of patients without arthritis (P=0.09). From seven patients with chronic arthritis, one had both positive anti-CCP and erosions. In the studied Iranian SLE patients, anti-CCP levels were higher in patients with arthritis than in those without arthritis. This study did not show any association of anti-CCP with erosion in SLE patients with arthritis. Ethnic and geographical variance may have influenced the results. More studies on chronic arthritis in SLE are needed to confirm this hypothesis.

Anti CCP and Anti MCV Antibodies are Marker of Arthritis in Systemic Lupus Erythematosus and Scleroderma

Anti CCP and Anti MCV Antibodies are Marker of Arthritis in Systemic Lupus Erythematosus and Scleroderma

Comparison of ultrasonographic joint and tendon findings in hands between early, treatment-naïve patients with systemic lupus erythematosus and rheumatoid arthritis.

Although both systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) may lead to joint deformity, SLE arthritis is typically non-erosive and often accompanied by Jaccoud's deformity. Therefore, we examined characteristics of joint and tendon lesions in patients with SLE and RA by ultrasonography. Fifteen treatment-naïve SLE patients and 40 treatment-naïve RA patients with joint symptoms were included in this study. The hand joints and related tendons were ultrasonographically examined using grey-scale (GS) and power Doppler (PD). Joint involvement was comparably observed in patients with SLE and RA (80% versus 95%, p = 0.119). However, tendon involvement was more frequent in SLE than in RA (93% versus 65%, p = 0.045), especially in the wrist joints (73% versus 40%, p = 0.037). When we investigated the intensity of US findings, the joint synovitis score (GS + PD) per affected joint was lower in SLE than RA (2.0 versus 2.6, p = 0.019), while tendon inflammation score was not significantly different (2.1 versus 2.2, p = 0.738). Finally, the examination of concordance between joint and tendon involvement in the same finger revealed that joint lesion appeared in only 49% of fingers having tendon involvement in the SLE group, which was significantly less than 74% in the RA group ( p = 0.010). Thus, as compared with RA, SLE arthropathy is characterized by the predominance of tenosynovitis/periextensor tendon inflammation, which is likely to develop independently from joint synovitis.

Novel mechanism of action of Anti-malarial drugs in the inhibition of Type I interferon production

Abstract Anti-malarial drugs (AMD) such as Hydroxychloroquine (HCQ) and Quinacrine (QC) are effective in the treatment of skin rash and arthritis in systemic lupus erythematosus (SLE). However which mechanism(s) are responsible for their beneficial action is uncertain. Type I interferon, (IFN-I) is strongly implicated in the pathogenesis of SLE and ‘interferonopathies’ such as Aicardi-Goutieres Syndrome (AGS). A new DNA activated IFN-I pathway, cyclic GMP-AMP (cGAMP) synthase (cGAS), was recently discovered and linked to AGS and mouse models of Lupus. In silico screening of drug libraries identified several antimalarial drugs (AMD) which could potentially inhibit cGAS activity by interacting with cGAS/DNA dimer complex. Electrophoretic Mobility Shift Assay revealed that AMD disrupted the double stranded DNA-cGAS complex in a dose dependent manner. These AMD also inhibited IFN-I expression in THP1 cells transfected with dsDNA and in 293T cells transfected with cGAS/STING plasmids validating that cGAS is a target of AMD. We synthesized several new AMD. One of these compounds, X6, had excellent water solubility and cell penetration. X6 localized to the cytosol and had a lower toxicity profile compared to QC. Biochemical and cellular assay revealed that X6 was a more potent inhibitor of IFN-I production than HCQ. Our studies identify new DNA sensor cGAS as a target of AMD activity, which provide a novel mechanism of action of these AMD. We have synthesized new AMD like drugs that are also able to inhibit cGAS as well as Toll pathways. These drugs could be beneficial for the treatment of AGS and/or Lupus.

Predictors of arthritis in pediatric patients with lupus.

BackgroundArthritis is one of the most common manifestations of systemic lupus erythematosus (SLE). Although typically non-erosive and non-deforming, children with SLE arthritis can have significant morbidity with decreased quality of life. Our goal was to identify potential clinical and laboratory predictors of arthritis in a cohort of pediatric patients with SLE.MethodsWe performed a cohort study of incident and prevalent patients with SLE aged ≤ 19 years. In cross sectional analysis, we compared demographic and clinical characteristics at initial clinic presentation between patients with arthritis noted at any time during follow-up and those without arthritis. We performed time to event analysis using Cox proportional hazard ratios to identify predictors of arthritis, clustering for repeated measures.ResultsForty seven children and adolescents with SLE were followed in the cohort, 91 % female and 68 % Black. In cross-sectional analyses, presence of malar rash was associated with arthritis. In longitudinal analyses, controlling for gender and race, increased age (HR: 1.4, 95 % CI: 1.1–1.7), malar rash (HR: 2.1, 95 % CI: 1.1–3.6), and presence of RNP antibodies (HR: 1.9, 95 % CI: 1.1–3.4) were predictive of arthritis. When controlling for gender, race, and medication use, anemia (HR: 8.5, 95 % CI: 2.9–24.2) and thrombocytopenia (HR: 6.1, 95 % CI: 2.4–15.6) were associated with increased risk of arthritis.ConclusionsWe identified markers predictive of arthritis in a longitudinal cohort of children with SLE. The recognition of these markers may help clinicians identify patients at risk for arthritis before its onset thus improving quality of life in children with SLE.

Anti-cyclic citrullinated peptide antibody as a marker of erosive arthritis in patients with systemic lupus erythematosus: a systematic review and meta-analysis

Anti-cyclic citrullinated peptide (CCP) antibody is an established marker in the diagnosis and prognostication of rheumatoid arthritis (RA). Infrequently, systemic lupus erythematosus (SLE) patients also develop a deforming erosive arthritis, similar to that of RA. Our objective was to determine whether anti-CCP antibody is a useful marker of erosive disease in SLE patients presenting with arthritis. Electronic databases EMBASE, MEDLINE and non-indexed MEDLINE citations were searched through April 11, 2014, using the outlined key terms. Studies meeting predefined inclusion and exclusion criteria were reviewed. Two reviewers independently assessed the quality of included articles using previously described criteria. The DerSimonian-Laird random effects model was used to calculate pooled sensitivity and specificity of anti-CCP antibody for erosive arthritis in SLE. Seven articles met inclusion and exclusion criteria. A total of 609 SLE patients with arthritis were identified, 70 of whom had erosive disease. Pooled sensitivity and specificity of anti-CCP antibody for erosive arthritis was 47.8% (95% CI, 26.2%-70.2%) and 91.8% (95% CI, 78.4%-97.2%), respectively. Our findings suggest that anti-CCP antibody is a highly specific marker for erosive arthritis in SLE. Longitudinal prospective studies are needed to determine if anti-CCP antibody can be used as a predictor of erosive disease.

AB1020 Ultrasonographic Evaluation of Articular Manifestations in Systemic Lupus Erythmatosus

BackgroundUltrasonography is widely used in the evaluation of joint lesions in rheumatoid arthritis (RA). While arthritis in systemic lupus erythematosus (SLE), unlike that in RA, is usually non-erosive and often...

How to treat refractory arthritis in lupus?

Arthritis in systemic lupus erythematosus (SLE) is episodic and self-limited in most patients. However, in some cases, refractory joint problems occur and may be poorly controlled by NSAIDs and other treatments. Damage to joints and to other organs must be considered when making any decision to prescribe such other treatments. In the context of new and potent biodrugs, we have reviewed and analysed here all Medline published data on arthritis treatment in SLE, as well as the French recommendations (Protocol national de diagnostic et de soins [PNDS] and Club Rhumatismes et Inflammation [CRI]). In SLE patients with isolated, intermittent joint symptoms, short courses of NSAIDs should be used as the first-line treatment. If joint symptoms are more severe or recurrent, a combination of low-dose corticosteroids (≤10mg/day) and antimalarial drugs is recommended. Corticosteroid infiltrations may be useful on occasions, in cases of persistent localised arthritis. If joint symptoms persist, treatment indications depend on the other organs affected. In joint forms that are refractory to treatment or corticodependent and requiring an unacceptable dose of prednisone in a patient with confirmed compliance with treatment, methotrexate should be proposed initially, in combination with antimalarial drugs. In cases of treatment failure or intolerance, mycophenolate mofetil or even azathioprine may be considered as an alternative treatment. As a last resort, after having weighed up the individual benefit-risk ratio, leflunomide, belimumab, rituximab or abatacept may be considered, on a case-by-case basis, and anti-TNF antibodies may be considered in exceptional cases.

Pediatric Systemic Lupus Erythematosus: More Than a Positive Antinuclear Antibody

Based on strong research evidence and consensus, the most common disease manifestations at diagnosis of pSLE are constitutional symptoms, arthritis, and malar rash. Based on some research evidence and consensus, patients with pSLE tend to have major organ system involvement (renal/central nervous system) and a greater disease burden compared with adults. Despite these findings, mortality is low. Based on some research evidence and consensus, the diagnosis of pSLE is unlikely if the ANA is negative, and most patients with SLE have a positive ANA at a titer ≥1:160. Based on strong research evidence, both MMF and cyclophosphamide can be used for induction therapy in class III and IV lupus nephritis. Based on strong research evidence, patients with SLE and anticardiolipin antibodies or LA have a two and six times greater risk of venous thrombosis, respectively, compared with patients with SLE without antiphospholipid antibodies. Based on strong research evidence, patients with pSLE have a higher risk for subclinical atherosclerosis when there is weight-adjusted prednisone use, azathioprine use, increasing age, male gender, high BMI, abnormal creatinine clearance, and elevated lipoprotein(a) levels.