To develop recommendations for the diagnosis, prevention and treatment of neuropsychiatric systemic lupus erythematosus (NPSLE) manifestations.
The authors compiled questions on prevalence and risk ...factors, diagnosis and monitoring, therapy and prognosis of NPSLE. A systematic literature search was performed and evidence was categorised based on sample size and study design.
Systemic lupus erythematosus (SLE) patients are at increased risk of several neuropsychiatric manifestations. Common (cumulative incidence > 5%) manifestations include cerebrovascular disease (CVD) and seizures; relatively uncommon (1-5%) are severe cognitive dysfunction, major depression, acute confusional state (ACS), peripheral nervous disorders psychosis. Strong risk factors (at least fivefold increased risk) are previous or concurrent severe NPSLE (for cognitive dysfunction, seizures) and antiphospholipid antibodies (for CVD, seizures, chorea). The diagnostic work-up of suspected NPSLE is comparable to that in patients without SLE who present with the same manifestations, and aims to exclude causes unrelated to SLE. Investigations include cerebrospinal fluid analysis (to exclude central nervous system infection), EEG (to diagnose seizure disorder), neuropsychological tests (to assess cognitive dysfunction), nerve conduction studies (for peripheral neuropathy) and MRI (T1/T2, fluid-attenuating inversion recovery, diffusion-weighted imaging, enhanced T1 sequence). Glucocorticoids and immunosuppressive therapy are indicated when NPSLE is thought to reflect an inflammatory process (optic neuritis, transverse myelitis, peripheral neuropathy, refractory seizures, psychosis, ACS) and in the presence of generalised lupus activity. Antiplatelet/anticoagulation therapy is indicated when manifestations are related to antiphospholipid antibodies, particularly thrombotic CVD.
Neuropsychiatric manifestations in SLE patients should be first evaluated and treated as in patients without SLE, and secondarily attributed to SLE and treated accordingly.
IntroductionLoneliness is prevalent among patients with inflammatory rheumatic diseases (IRDs), however the COVID-19 pandemic may intensify loneliness among patients with IRDs, as they are at higher ...risk of severe illness. Early evidence suggests that this was indeed the case during the early stages; however, it remains largely unknown whether loneliness remains present and what factors are associated. The objective of the present study was to identify risk and protective factors associated with loneliness in individuals living with IRDs in the later stage of the COVID-19 pandemic.MethodsData from an online cross-sectional survey study of individuals with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) between May 2022 and February 2023. Participants were recruited from a list of patients already enrolled in a multi-site longitudinal observation study. All participants provided informed consent. Loneliness was assessed with the University of California, Los Angeles Loneliness Scale (Version 3), Short Form 3-item (UCLA- LS3-SF3). The Impact of Event Scale-Revised (IES-R) assessed post-traumatic stress symptoms (PTSS) caused by the COVID-19 pandemic. The Patient Health Questionnaire-8 (PHQ-8) measured symptoms of depression. Resilience and concerns related to COVID-19 were also assessed. Descriptive statistics and linear regressions were conducted.ResultsThe study population was n = 160 (SLE = 102, RA = 58), mean age 60.1 years (±13) and 21.9% (n=35) were men. Almost one third (28.1%) reported moderate to severe loneliness. (UCLA-LS3-SF3 score ≥6), with statistically significant difference between both disease groups (SLE = 36.3%; RA= 13.8%). Among participants with SLE, gender (men), psychological burden from the COVID-19 pandemic, and higher depressive symptoms were independently associated with greater loneliness, accounting for 38% of the variance (table 1). Among individuals living with RA, identifying as female and greater psychological burden from the COVID-19 pandemic were independently associated with greater loneliness, accounting for 55% of the variance.DiscussionThe results suggest that special attention to men with SLE and women with RA is needed when targeting loneliness in people with IRDs. More attention to strategies to decrease depressive symptoms and the psychological burden of the pandemic in patients living with IRDs are needed in future public health crises.Abstract 1403 Table 1Factors associated with loneliness during the later stages of the COVID-19 pandemic in people with IRDs Parameter Β1 p-value 95% C.I. Lower Upper SLE Age .013 .877 −.022 .025 Gender − .178 .032 - 2.55 − .199 Psychological Burden of pandemic .212 .035 .002 .063 Covid-19 concerns .062 .514 −.025 .050 Depression .333 .002 .046 .208 Resilience −.154 .136 −.903 .125 RA Age .022 .855 −.029 .035 Gender .229 .032 .051 1.12 Psychological Burden of pandemic .380 .014 .010 .081 Covid-19 concerns .240 .114 −.010 .087 Depression .109 .352 −.046 .127 Resilience −.170 .100 −.707 .063 1Standardized beta coefficients. CI = confidence interval.
We studied damage accrual and factors determining development and progression of damage in an international cohort of systemic lupus erythematosus (SLE) patients.
The Systemic Lupus International ...Collaborating Clinics (SLICC) Inception Cohort recruited patients within 15 months of developing four or more 1997 American College of Rheumatology (ACR) criteria for SLE; the SLICC/ACR damage index (SDI) was measured annually. We assessed relative rates of transition using maximum likelihood estimation in a multistate model. The Kaplan-Meier method estimated the probabilities for time to first increase in SDI score and Cox regression analysis was used to assess mortality.
We recruited 1722 patients; mean (SD) age 35.0 (13.4) years at cohort entry. Patients with damage at enrolment were more likely to have further worsening of SDI (SDI 0 vs ≥1; p<0.001). Age, USA African race/ethnicity, SLEDAI-2K score, steroid use and hypertension were associated with transition from no damage to damage, and increase(s) in pre-existing damage. Male gender (relative transition rates (95% CI) 1.48 (1.06 to 2.08)) and USA Caucasian race/ethnicity (1.63 (1.08 to 2.47)) were associated with SDI 0 to ≥1 transitions; Asian race/ethnicity patients had lower rates of new damage (0.60 (0.39 to 0.93)). Antimalarial use was associated with lower rates of increases in pre-existing damage (0.63 (0.44 to 0.89)). Damage was associated with future mortality (HR (95% CI) 1.46 (1.18 to 1.81) per SDI point).
Damage in SLE predicts future damage accrual and mortality. We identified several potentially modifiable risk factors for damage accrual; an integrated strategy to address these may improve long-term outcomes.
PurposeThe efficacy of antimalarials, especially hydroxychloroquine (HCQ), in preventing flares of systemic lupus erythematosus (SLE) is well demonstrated, but its effectiveness is impaired by ...non-adherence to treatment, reported to vary between 3% and 85%.We aimed to assess the associations of baseline severe non-adherence to HCQ, objectively assessed by HCQ serum levels, and risks of SLE flares, damage, and mortality over 5 years of follow-up.MethodsThe SLICC Inception Cohort is a multicentric prospective study of SLE patients from 31 centers in 11 countries. Patients were enrolled within 15 months of recognition of SLE (1997 ACR classification criteria). Serum HCQ levels of patients with HCQ prescription for at least 3 months, sampled at enrollment (or, if unavailable, during the first-year follow-up visits), were centrally measured. Severe non-adherence was defined by a serum HCQ level <106 ng/mL for a daily prescribed HCQ dose of 400 mg, and <53 ng/mL for a daily HCQ dose of 200 mg, respectively (1). SLE flare was defined by the occurrence of one of the following events within the first year following serum collection: (a) increase of at least four point in the SLEDAI-2K; (b) new start in prednisone (oral or pulse) or immunosuppressive agent; (c) a new renal involvement (active nephritis, nephrotic syndrome). Association between severe non-adherence and SLE flare was assessed with logistic regression models, further adjusted on potential confounders. Damage was assessed by the time until an increase ≥1 in the SLICC damage index (SDI), within the 5 years following HCQ measurement. Associations between severe non-adherence and either damage or mortality (from all cause) within 5 years following HCQ measurement were assessed with Cox proportional hazard models, adjusted on sex, education, and potential confounders.ResultsOf 1849 cohort subjects, 660 patients (88% women) were included. Median interquartile range serum HCQ level was 388 ng/mL (244–566) and 48 patients (7.3%) had severe HCQ non-adherence. No factors were clearly associated with severe non-adherence. A SLE flare occurred in 191 (28.9%) patients within the first year (28 58.3% non-adherent patients versus 163 26.6% other patients). In multivariate analysis, severe nonadherence was independently associated with the risk of flare (OR= 3.32; 95% CI 1.78–6.28).Within five years, 167 patients (25.3%) had ≥1 point increase of SDI. Severe on-adherence was associated with an increase in the SDI within each of the first 3 years (HR 1.92 at 3 years; 95% CI 1.05–3.50).Eleven patients died within 5 years, including 3 with severe non-adherence (unadjusted HR 5.41; 95% CI 1.43–20.39).Abstract S15.2 Figure 1Risk of damage, defined by a ≥1-point increase in SLICC ACR damage index, according to severe non-adherence to hydroxychloroquine (n=660)ConclusionsIn this large multicentric international prospective cohort, severe non-adherence was independently associated with the risk of SLE flare in the following year, with early damage, and 5-year mortality. As severe non-adherence is often unknown by the physician and since no predictive clinical or biological factors were identified, our results suggest the benefits of testing to detect severe non-adherence, to identify the patients at risk.
To determine the frequency, accrual, attribution and outcome of neuropsychiatric (NP) events and impact on quality of life over 3 years in a large inception cohort of patients with systemic lupus ...erythematosus (SLE).
The study was conducted by the Systemic Lupus International Collaborating Clinics. Patients were enrolled within 15 months of SLE diagnosis. NP events were identified using the American College of Rheumatology case definitions, and decision rules were derived to determine the proportion of NP disease attributable to SLE. The outcome of NP events was recorded and patient-perceived impact determined by the SF-36.
1206 patients (89.6% female) with a mean (+/-SD) age of 34.5+/-13.2 years were included in the study. The mean disease duration at enrollment was 5.4+/-4.2 months. Over a mean follow-up of 1.9+/-1.2 years, 486/1206 (40.3%) patients had > or =1 NP events, which were attributed to SLE in 13.0-23.6% of patients using two a priori decision rules. The frequency of individual NP events varied from 47.1% (headache) to 0% (myasthenia gravis). The outcome was significantly better for those NP events attributed to SLE, especially if they occurred within 1.5 years of the diagnosis of SLE. Patients with NP events, regardless of attribution, had significantly lower summary scores for both mental and physical health over the study.
NP events in patients with SLE are of variable frequency, most commonly present early in the disease course and adversely impact patients' quality of life over time. Events attributed to non-SLE causes are more common than those due to SLE, although the latter have a more favourable outcome.
Antiphospholipid syndrome: an overview Hanly, John G
Canadian Medical Association journal (CMAJ),
2003-Jun-24, 20030624, Letnik:
168, Številka:
13
Journal Article
Recenzirano
Antiphospholipid antibodies are a heterogeneous group of autoantibodies that are detected by immunoassays and functional coagulation tests. The antigenic targets are negatively charged phospholipids ...and serum phospholipid-binding proteins. The latter antibodies are frequently associated with thrombosis, fetal loss and other clinical manifestations of the antiphospholipid syndrome. These antibodies are felt to be etiologically important in the syndrome, although the precise pathogenic mechanisms are still being determined. Proposed mechanisms include antibody-mediated interference with coagulation homeostasis, activation of platelets and endothelial cells and a T-cell immune response to serum phospholipid-binding proteins. The mainstay of therapy is anticoagulation, whereas immunosuppression is ineffective.
Background and aimsTo determine the frequency, associations and outcomes of cerebrovascular events (CerVEs) in a multi-ethnic/racial, prospective, inception cohort of SLE patients.MethodsPatients ...were assessed annually for 19 neuropsychiatric events including 5 types of CerVEs: (i) Stroke; (ii) Transient ischemia; (iii) Chronic multifocal ischemia; (iv) Subarachnoid and intracranial haemorrhage; (v) Sinus thrombosis. Global disease activity (SLEDAI-2K), SLICC/ACR damage index (SDI) and SF-36 subscale, mental (MCS) and physical (PCS) component summary scores were collected. Time to event, linear and logistic regressions and multi-state models were used as appropriate.ResultsOf 1826 SLE patients, 88.8% were female, 48.8% Caucasian, mean±SD age 35.1±13.3 years, disease duration 5.6±4.2 months and follow-up 6.6±4.1 years. CerVEs were the fourth most frequent NP event: 82/1,826 (4.5%) patients had 109 events and 103/109 (94.5%) were attributed to SLE. The predominant events were stroke 60/109 (55.0%) and transient ischemia 28/109 (25.7%). CerVEs were associated with NP events attributed to SLE (HR (95% CI): (3.16; 1.73–5.75), non-SLE (2.60; 1.49–4.51) (p<0.001), African ancestry at US SLICC sites (2.04; 1.01–4.13) (p=0.047) and organ damage (p=0.041). Lupus anticoagulant increased the risk of first CerVE (1.77; 0.99–3.16). Physician assessment indicated resolution or improvement in the majority but patients reported a sustained reduction in SF-36 summary and subscale scores following CerVEs (p<0.0001).ConclusionsCerVEs, the fourth most frequent NP event in SLE, are usually attributable to lupus early in the disease course. In contrast to good physician reported outcomes, patients report a sustained reduction in health related quality of life following CerVEs.
PDF
