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Lupus psychosis is a rare, potentially devastating, but treatable manifestation of systemic lupus erythematosus (SLE) that is associated with certain patient characteristics, analysis of data from a large inception cohort found.

Among 1,826 patients with SLE enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) network and followed for a mean of 7.4 years, 28 patients experienced 31 psychotic events (1.53%), according to John G. Hanly, MD, of Dalhousie University in Halifax, Nova Scotia, and colleagues.

Factors that were positively associated with lupus psychosis on a multivariate analysis included African ancestry (HR 4.59, 95% CI 1.79-11.76), previous SLE neuropsychiatric events (HR 3.59, 95% CI 1.16-11.14), male sex (HR 3, 95% CI 1.20-7.50), and younger age at the time of SLE diagnosis (per 10 years, HR 1.45, 95% CI 1.01-2.07), the researchers reported online in .

"Our findings confirm and expand upon the results of previous cross-sectional and historical studies of psychosis in SLE," Hanly and colleagues observed. "The outcome of lupus psychosis, as determined by both physicians and patients, was positive and emphasizes the importance of diagnosing and treating this rare manifestation of neuropsychiatric SLE," they wrote.

A further optimistic note was sounded by Michael D. Lockshin, MD, of the Hospital for Special Surgery in New York City, in an accompanying editorial. "Improved technologies in the fields of molecular immunology, blood-brain barrier function, and cognitive function, and new concepts like microglial metabolism and pruning are beginning to demystify the complexity of central nervous system SLE," Lockshin wrote.

Neuropsychiatric manifestations of SLE range from headache to seizures and stroke. Psychosis is one of the rarer manifestations, and is characterized by delusions and hallucinations, and has sometimes been associated with an autoantibody against ribosomal P. Little is known about its frequency, attribution, clinical patterns, or outcomes.

To address this knowledge gap, the SLICC network investigators analyzed data collected prospectively each year from 31 centers in 10 countries.

The definition of psychosis associated with SLE established by the American College of Rheumatology requires "delusions or hallucinations without insight; causing clinical distress or impairment in social, occupational, or other relevant areas of functioning; disturbance should not occur exclusively during delirium; and not better accounted for by another mental disorder."

Attribution of the psychosis to SLE considered the temporal association of the event in relation to SLE diagnosis, and also considered concurrent non-SLE factors including "exclusions," defined as psychotic disorders unrelated to SLE, substance or drug-induce psychosis, and psychological reactions to SLE; as well as "associations," which included marked psychosocial stress, corticosteroid use, and common neuropsychiatric events in the general population such as headache and mild depression.

Attribution model A, which was the most stringent, required that the psychotic event occur within the enrollment window (from 6 months before diagnosis to enrollment in the cohort) and have no exclusions or associations, while attribution model B, the least stringent, required only that the event occur within 10 years of SLE diagnosis and have no exclusions.

Covariates in the analysis included, sex, race/ethnicity, number of other ACR lupus criteria, age at diagnosis, autoantibodies, SLE Disease Activity Index (SLEDAI), and SLE Damage Index (SDI).

Almost 90% of patients were women, half were white, mean SLEDAI score was 5.3, and SDI was 0.32.

Any type of neuropsychiatric disorder was reported in 52.1% of patients, and represented the entire spectrum of ACR neuropsychiatric events.

Among the 28 patients who had psychosis, 26 had only one episode, while one had two and another had three episodes.

The majority of events were attributable to SLE, at 54% using attribution model A and 89% using attribution model B. Most patients (80%) experiencing psychosis had the initial episode during the year prior to SLE diagnosis or in the first 3 years after.

A univariate analysis found associations between lupus psychosis and male sex (HR 2.58, 95% CI 1.04-6.41), anti-ribosomal P antibodies at baseline (HR 3.31, 95% CI 1.19-9.21), central neuropsychiatric events (HR 3.86, 95% CI 1.27-11.70), diffuse neuropsychiatric events (HR 6.36, 95% CI 2.12-19.12), younger age at diagnosis (per 10 years, HR 1.36, 95% CI 1-1.88), and African ancestry (HR 4.80, 95% CI 1.86-12.40).

Treatment of the individual patients was at the discretion of their rheumatologist, and included corticosteroids in 82.1%, with a mean prednisone dose of 21.9 mg/day, immunosuppressants such as cyclophosphamide, azathioprine, methotrexate, and mycophenolate mofetil (CellCept) in 60.7%, biologics in 3.6%, antipsychotic drugs in 67.9%, and antidepressants in 39.3%.

More than 80% of the psychotic events had resolved by the second annual follow-up visit after the event onset. Quality of life, as measured on the Short Form 36, improved substantially after resolution of the psychosis, with mean differences of 7.01 on the mental health component and 4.34 on the physical component. This represented a "remarkable reversal" for patient-reported quality of life, the authors pointed out.

A limitation of the study was its observational design, which precluded comparisons of efficacy for treatment approaches.