Psychosis in Systemic Lupus Erythematosus: Results from an International, Inception Cohort Study

Abstract

Background/Purpose: Psychosis, one of the rarer neuropsychiatric (NP) events in lupus patients, features in both the ACR and Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE. Our objective was to determine, in a multi-ethnic/racial, prospective SLE inception cohort, the frequency, attribution, clinical and autoantibody associations with lupus psychosis and the outcome as assessed by physicians and patients.

Methods: A prospective study of new onset SLE patients was performed by an international network of 32 academic centers in 11 countries. Patients were evaluated at enrollment and annually for up to 17 years. Data were collected at each assessment on 19 NP events including psychosis, as per the ACR case definitions for NPSLE. Pre-defined decision rules were used to attribute the events to SLE and non-SLE causes. Demographic features, medications, SLE disease activity index-2000 (SLEDAI-2K), SLICC/ACR damage index (SDI) and SF-36 mental (MCS) and physical (PCS) component summary scores were also recorded. Plasma lupus anticoagulant (LAC), serum IgG anti-cardiolipin, anti-β2 glycoprotein-I, anti-ribosomal P (anti-P) and anti-NR2 glutamate receptor antibodies were measured. Descriptive statistics, time to event analysis and linear regressions were used as appropriate and multivariable models included demographic, clinical and serological variables.

Results: Of 1,826 SLE patients, 88.8% were female, 48.8% Caucasian. The mean±SD age was 35.1±13.3 years, disease duration 5.6±4.2 months and follow-up 7.4±4.5 years. There were 31 psychotic events in 28/1,826 (1.53%) patients and most patients [(26/28; 93%)] had a single event. In the majority of patients [25/28; (89%)] and events [28/31; (90%)] psychosis was attributed to SLE, usually within 3 years of SLE diagnosis. Concurrent therapies included corticosteroids 23/28 (82.1%) with a mean (SD) prednisone dose of 21.9 (14.9) mg/day, immunosuppressants 17/28 (60.7%), biologics 1/28 (3.6%), antipsychotic drugs 19/28 (67.9%) and antidepressants 11/28 (39.3%). In multivariable analyses, positive associations [hazard ratio and 95% confidence interval [HR (95%CI)] with lupus psychosis were prior SLE NP events [3.59, (1.16, 11.14), male sex [3.0, (1.20, 7.50)], younger age at SLE diagnosis [(per 10 years younger), 1.45 (1.01, 2.07)] and African ancestry [4.59 (1.79, 11.76)]. There was no association with SLE disease activity, organ damage or autoantibodies. Patients with psychosis had significantly lower concurrent SF-36 summary scores compared to patients without NP events (MCS: 38.9±13.3 vs. 48.9±10.7; PCS: 38.9±11.0 vs. 44.1±10.9; p<0.001). By physician assessment 80% of psychotic events resolved by the second annual assessment following onset. For these patients there was a concurrent clinically significant improvement in both MCS (45.5±14.1) and PCS scores (43.2±10.9).

Conclusion: Psychosis is an infrequent but important manifestation of NPSLE. It occurs early after SLE onset, is usually mono-phasic and has a significant negative impact on health status. As determined by patient and physician report, the outcome is favorable for most patients.