ObjectivesTo develop recommendations for the diagnosis, prevention and treatment of neuropsychiatric systemic lupus erythematosus (NPSLE) manifestations. Methods 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. Results 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 fi vefold 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 fl uid 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, fl uid-attenuating inversion recovery, diffusion-weighted imaging, enhanced T1 sequence). Glucocorticoids and immunosuppressive therapy are indicated when NPSLE is thought to refl ect an infl ammatory 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. Conclusions Neuropsychiatric manifestations in SLE patients should be fi rst evaluated and treated as in patients without SLE, and secondarily attributed to SLE and treated accordingly. involve the central and the peripheral nervous system and that range from overt manifestations such as stroke, seizures and psychosis, to more subtle abnormalities of cognitive function (see supplementary table S1, available online only). Multiple pathological mechanisms are implicated in NPSLE, including antiphospholipid or other autoantibodymediated vascular or neuronal injury, intrathecal production of infl ammatory mediators and accelerated atherosclerosis. Despite substantial advances in the understanding of lupus, NPSLE continues to pose diagnostic and therapeutic challenges to practising physicians. The indicated diagnostic work-up remains unclear, therapies are empiric, and the prognosis after an neuropsychiatric event is often diffi cult to determine. We sought to develop recommendations for the management of systemic lupus erythematosus (SLE) patients presenting with neuropsychiatric manifestations using an evidencebased approach followed by exper...

Objectives 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 SLE patients. Methods 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 ACR 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. Results There were 1206 patients (89.6% female) with a mean (±SD) age of 34.5±13.2 years. 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 ≥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. Conclusions NP events in SLE patients are variable in 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.

Overall and as used in routine care against RA, TNF antagonists are not associated with any major further increase in the already elevated lymphoma occurrence in RA. Changes in the selection of patients for treatment may influence the observed risk.

Objective. To examine the relationship between changes in anti-double-stranded DNA (anti-dsDNA) antibody levels and the risk of renal flare in patients with systemic lupus erythematosus (SLE), using data from 2 randomized, controlled trials.Methods. Analyses were based on 487 patients with SLE and a history of lupus nephritis who had an anti-dsDNA antibody titer >15 IU/ml at baseline, as measured by Farr assay. Results are presented for the combined population of patients, the placebo arms, and the drug treatment arms in which a dsDNA-based bioconjugate (abetimus sodium; LJP 394) was used.Results. Changes in anti-dsDNA antibody levels were inversely correlated with changes in the C3 level (P < 0.0001 in both trials). Cox proportional hazards regression models showed that changes in anti-dsDNA antibody levels correlated with the risk of renal flare. The models predicted that a point estimate of a 50% reduction in anti-dsDNA antibody levels is associated with a 52% reduction (95% confidence interval [95% CI] 26-68%, nominal P ‫؍‬ 0.0007) and a 53% reduction (95% CI 33-69%, nominal P < 0.0001) in the risk of renal flare in the 2 trials, respectively. In the 2 trials, the incidence of renal flare was lower in patients with sustained reductions in anti-dsDNA antibodies (3.0% and 4.1%, respectively) than in patients with stable or increasing antibody levels (21.3% and 20.3%, respectively).Conclusion. Changes in anti-dsDNA antibody levels were directly correlated with the risk of renal flare and inversely correlated with changes in the C3 level. Reducing anti-dsDNA antibody levels may represent a therapeutic objective in SLE patients with lupus nephritis, because it is associated with a reduced risk of renal flare.Anti-double-stranded DNA (anti-dsDNA) antibodies are diagnostic for systemic lupus erythematosus (SLE) (1) and have been implicated in the underlying pathogenesis of SLE renal disease and other disease manifestations (2-7). Immune complexes containing anti-