Cognitive dysfunction improves in systemic lupus erythematosus: Results of a 10 years prospective study

Objective Cognitive impairment (CI) has been described in 3–80% of Systemic lupus erythematosus (SLE) patients but only short-term studies evaluated its over-time changes, suggesting that CI is usually a stable finding. We aimed at evaluating the changes of SLE-related CI in a 10-years prospective single center cohort study. Methods We evaluated 43 patients (M/F 5/38; mean age = 45.7±10.1 years; mean disease duration = 230.8±74.3 months) at baseline (T0) and after 10 years (T1). A test battery designed to detect fronto-subcortical dysfunction across five domains (memory, attention, abstract reasoning, executive and visuospatial function) was administered. A global cognitive dysfunction score (GCD) was obtained and associated with clinical and laboratory features. Results Prevalence of CI was 20.9% at T0 and 13.9% at T1 (P = NS). This impairment was prevalently mild at T0 (55.5%) and mild or moderate at T1 (36.3% for both degrees). After 10 years, CI improved in 50% of patients, while 10% worsened. Impaired memory (P = 0.02), executive functions (P = 0.02) and abstract reasoning (P = 0.03) were associated with dyslipidemia at T0. Worsening of visuospatial functions was significantly associated with dyslipidemia and Lupus Anticoagulant (P = 0.04 for both parameters). Finally, GCD significantly correlated with chronic damage measured by SLICC/damage index at T0 (r = 0.3; P = 0.04) and T1 (r = 0.3; P = 0.03). Conclusions For the first time, we assessed CI changes over 10-years in SLE. CI improved in the majority of the patients. Furthermore, we observed an improvement of the overall cognitive functions. These results could suggest that an appropriate management of the disease during the follow-up could be able to control SLE-related CI

Pragmatic language dysfunction in systemic lupus erythematosus patients: Results from a single center Italian study

Cognitive impairment (CI) in systemic lupus erythematosus (SLE) is a frequent neuropsychiatric manifestation affecting several domains, even in apparently asymptomatic patients. Current research revealed that the typical CI pattern affects frontal-subcortical circuit and thus executive functions. The impairment of non-literal language or pragmatic language (PL), including metaphors, idioms, inferences or irony has been well described in several conditions such as autism disorders, Parkinson's disease, brain injury and even in earlier phases of neurodegenerative processes. Even if PL neuro-anatomy remains controversial, correlation between executive dysfunctions and non-literal language involvement has been reported both in traumatic injury and mild cognitive impairment patients. Nonetheless, no specific study has been performed to evaluate PL impairment in SLE patients so far

Development of systemic autoimmune diseases in healthy subjects persistently positive for antiphospholipid antibodies. long-term follow-up study

We longitudinally followed a single-center cohort of anti-phospholipid (aPL) positive healthy subjects to evaluate the evolution to systemic autoimmune diseases (sAD) and to describe clinical and serological associated features. Since 2010, we have consecutively screened healthy subjects who were positive, in at least two consecutive determinations, for one or more aPL [anti-Cardiolipin (aCL) IgM/IgG, anti-Beta2Glycoprotein I (aB2GPI) IgM/IgG, Lupus Anticoagulant (LA)]. All subjects were evaluated every six months, or in accordance with the patient's clinical course, in order to record the development of clinical and laboratory features suggestive for sAD. Ninety-five subjects [M/F 20/75, median age at first determination 46 years, Interquartile Range (IQR) 19] were enrolled. Thirty-three subjects (34.7%) were positive for only one aPL [15 (15.8%) for aCL, 15 (15.8%) for LA, and 5 (5.3%) for aB2GPI]; 37 (38.9%) had double positivity [32 (33.6%) for aCL and aB2GPI; 5 (5.3%) for aCL and LA], 23 (24.2%) had triple positivity. We prospectively followed up our cohort for a median period of 72 months (IQR 84). During a total follow-up of 7692 person-months, we found an absolute risk for sAD development equal to 1.8%. Specifically, 14 (14.7%) patients developed a sAD: in four patients (4.2%), after developing a thrombotic event, an antiphospholipid syndrome was diagnosed, 7 (7.4%) patients developed an Undifferentiated Connective Tissue Disease after a median period of 76 months (IQR 75.5), and lastly, three (3.1%) patients could be classified as affected by Systemic Lupus Erythematosus according to the ACR/EULAR 2019 criteria. The presence of triple positivity status resulted in being significantly associated with the progression to sAD (p-value = 0.03). In conclusion, we observed the development of sAD in almost 15% of aPL positive subjects. Triple positivity was significantly associated with this progression, suggesting a possible role as biomarker for this condition. Thus, our results could suggest the need for periodic follow-up for such patients to assess early diagnosis and treatment

Can We Identify Who Gets Benefit or Harm from Mycophenolate Mofetil in Systemic Lupus Erythematosus?:A Systematic Review

AbstractObjectives We aimed to summarize the evidence examining factors that predict differential response to mycophenolate mofetil (MMF) in systemic lupus erythematosus (SLE). Methods Systematic searches of randomized clinical trials (RCT) to identify predictors of the effects of MMF (moderators), and cohort studies to explore prognostic factors associated with MMF outcomes (response, relapse or adverse events) were performed. Two reviewers independently assessed the methodological quality of RCTs using the Cochrane Collaboration risk of bias tool and cohort studies using the QUality In Prognosis Studies tool. The quality of subgroup analysis, providing evidence for moderation, was evaluated. The Grading of Recommendations Assessment, Development, and Evaluation working group approach summarized the quality of evidence (QoE), considering the risk of bias, imprecision, inconsistency, indirectness, and publication bias. Results From 26 studies (7 RCTs and 13 cohort studies) we found low QoE evidence for Black/Hispanic race/ethnicity predicting better renal responses to MMF in lupus nephritis (LN) from one RCT. There was low QoE evidence from cohort studies that a higher baseline creatinine and membranous features on renal biopsy were associated with poorer responses in LN. There was very low QoE for other moderators or prognostic factors associated with MMF treatment outcomes. QoE from RCTs was affected by exploratory or insufficient evidence from subgroup analysis and in both study types high risk of bias, indirectness and imprecision also affected QoE. Conclusions In SLE, evidence for predictors of response to MMF is limited and none can be recommended for use in routine clinical practice. Specific studies of predictors measured at baseline and during treatment are needed with ‘a priori’ hypotheses based on preliminary evidence to date and with sufficient power to determine which factors can be employed in clinical decision making

Single-centre retrospective analysis of the best timing for the QTc interval length assessment in neonates

Objective To evaluate the best timing for ECG screening in order to diagnose long QT syndrome and lower, at the same time, the false positives.Design We retrospectively evaluated the corrected QT (QTc) interval in the clinical reports of the ECG screening performed, as per internal protocol.Setting An outpatient setting in our Unit of Neonatology and Pediatrics, Santa Maria Goretti Hospital in Latina, Italy.Patients We enrolled 3467 healthy neonates between 14 and 30 days of life.Interventions The newborns with abnormal QTc interval were invited to subsequent revaluation every 21 days, until normalisation or necessity to refer to a tertiary paediatric cardiology centre.Main outcome measures Difference in QTc according to patients’ characteristics and number of false positives at second ECG evaluation.Results At first evaluation, 249 (7.2%) newborns had prolonged QTc. We did not find any significant difference in the QTc length according to gestational age (p=0.40) and birth weight (p=0.81). As expected, girls had longer QTc than boys (p=0.01). Only 11 out of 240 (4.6%) and 1 out of 238 infants (0.4%) had persistently prolonged QTc at second and third ECG evaluation, respectively. The QTc decreased significantly at second (p<0.0001) and third evaluation (p=0.0035).Conclusions In our study, we showed that a single screening performed in healthy infants after 60 days of life could reduce the risk of false positives, with a beneficial impact on public national health system and the chance to start early therapy in case of long QT syndrome

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

Predictive and prognostic factors influencing outcomes of rituximab therapy in systemic lupus erythematosus (SLE): a systematic review

The clinical outcomes following rituximab (RTX) treatment in patients with systemic lupus erythematosus (SLE) is highly variable. We aimed to identify predictive and prognostic factors associated with RTX therapy outcomes in patients with SLE

Breastfeeding in women affected by systemic lupus erythematosus. rate, duration and associated factors

Objective: Breastfeeding is a crucial moment for both mothers and child, providing a beneficial effect on child survival, nutrition, development and on maternal health. Despite the prevalent involvement of childbearing women in systemic lupus erythematosus (SLE), breastfeeding is still a neglected topic. The objective of this study was to evaluate breastfeeding frequency, duration and associated factors in SLE women. Methods: We consecutively enrolled SLE pregnant women reporting demographic, clinical, serological, gynaecological and obstetric data. Breastfeeding experience was evaluated by using a specific questionnaire. Disease activity was assessed before and during pregnancy as well as during postpartum. Results: A total of 57 pregnancies in 43 SLE women were included in the present study. In almost all the pregnancies, mothers planned to breastfeed their child (96.5%) and forty-one (71.9%) actually did breastfeed. The median time of breastfeeding was 3 months (IQR 7). Non-breastfeeding women showed a more frequent caesarean section (p ¼ 0.0001), IUGR occurrence (p ¼ 0.004) and disease relapse (p ¼ 0.0001) after pregnancy. When comparing patients according with breastfeeding duration (cut-off 6 months), we found a significant more frequent smoking habitus (p ¼ 0.02), caesarean section (p ¼ 0.009), and joint involvement during postpartum (p ¼ 0.0001) in women breastfeeding for less than or equal to 6 months, together with higher median BMI (p ¼ 0.0001). Moreover, breastfeeding duration was positively associated with disease duration and hydroxychloroquine (HCQ) treatment during disease history, pregnancy and postpartum. Conclusions: SLE women didn’t show lower breastfeeding rate in comparison with general population but they presented higher prevalence of early discontinuation within three months. Early interruption was positively associated with smoking, BMI, joint involvement; meanwhile disease duration and HCQ treatment during postpartum were positively associated with a longer breastfeeding duration

Erosive arthritis in systemic lupus erythematosus: application of cluster analysis

Objectives: 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. Methods: 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. Results: 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. Conclusions: 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