Psychosis Is a Rare But Treatable Lupus Manifestation, Large International Study Shows

Ana Pena, PhD avatar

by Ana Pena, PhD |

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Psychosis and SLE

Psychosis is a rare manifestation of systemic lupus erythematosus (SLE) that generally appears early, in the year before or within the first three years after SLE onset. The disorder is generally treatable, with patients fully recovering and rarely relapsing, a large international prospective study shows.

Men, people of African ancestry, or those diagnosed with lupus at a younger age are at higher risk of having a psychotic manifestation, the data indicate.

The study, “Psychosis in Systemic Lupus Erythematosus,” was published in the journal Arthritis & Rheumatology.

Neuropsychiatric manifestations of SLE can include headache, seizures, and stroke. One of the rarest manifestations is lupus psychosis, a condition marked by delusions and hallucinations, which can dramatically affect a patient’s quality of life.

Because it is rare, little is known about the frequency, clinical patterns, or outcomes of lupus psychosis.

Recognizing this gap, an international team of researchers with the Systemic Lupus International Collaborating Clinics (SLICC) conducted a prospective study to determine the frequency, clinical features, and short- and long-term outcomes of lupus psychosis.

SLICC is a network of 53 investigators in 43 academic medical centers in 16 countries.

To get a broad picture of lupus psychosis, the study involved 1,826 patients, enrolled at 31 centers in 10 countries (U.S., Canada, U.K., Sweden, Spain, Denmark, Iceland, Turkey, Korea, and Mexico).

Data were collected at enrollment and annually and patients were followed for a mean of 7.4 years. Most were women (88.8%) and nearly half were Caucasian (48.8%); mean age was 35.1 years.

Researchers adopted the American College of Rheumatology (ACR) definition of psychosis: 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.

Patients whose psychosis was primary or reactive, due to depression or cognitive decline, or associated with medicines or illicit drugs were excluded.

Among the 1,826 patients, 28 experienced 31 psychotic events (1.53%) during study follow-up. Of these, 26 had one episode, one had two and one had three.

For most patients (80%), psychosis was attributed to SLE, and usually occurred the year before  diagnosis or within the first three years after.

Other factors linked to increased risk of lupus psychosis included having prior neuropsychiatric episodes associated with SLE and carrying anti-ribosomal P antibodies.

“This finding is not surprising — experienced clinicians might have guessed the result — but it does, for the first time, provide strong documentation for a field that otherwise lacks good information,” Michael D. Lockshin, MD, from New York’s Hospital for Special Surgery, wrote in an editorial accompanying the study.

The prescribed treatment varied, depending on each patient’s rheumatologist, and “on the overall needs of the patient and not only the psychotic events,” researchers stated.

The therapies included corticosteroids in 82.1% of the cases; immunosuppressants such as cyclophosphamide, azathioprine, methotrexate, and CellCept (mycophenolate mofetil) in 60.7%; antipsychotic drugs in 67.9%; antidepressants in 39.3%, and biologics in 3.6%.

After the initial episode, more than 80% of the events had resolved by the second annual follow-up visit, according to physician assessments.

After resolution of psychosis, patient-reported quality of life (measured by SF-36), substantially improved, both overall and in the mental health and physical components, representing a “remarkable reversal,” in the words of the researchers.

The findings “confirm and expand upon the results of previous cross-sectional and historical studies of psychosis in SLE” they said.

“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 said.

The authors point out that one limitation of the study is observational design, which “precludes determination of optimal therapeutic regimes for lupus psychosis but rather reflects current standard of care.”

Despite the study’s limitations, Lockshin states in his editorial that this research has offered valuable clinical information and provided answers to questions about lupus psychosis.

He said he believes that “major advances seem likely soon,” including technology improvements in molecular immunology and neurosciences that “are beginning to demystify the complexity of central nervous system [brain and spinal cord] SLE.”