SNOWMASS, COLO. – The pendulum appears to be swinging away from the broad definition of neuropsychiatric systemic lupus erythematosus advocated by the American College of Rheumatology in a landmark 1999 report in favor of a much more restrictive set of manifestations, according to Dr. W. Joseph McCune.

The ACR list of 19 neuropsychiatric syndromes attributable to SLE includes headache, mood disorders, cognitive dysfunction, and anxiety disorders (Arthritis Rheum. 1999;42:599-608). The problem is that these features are quite common among individuals without SLE, and attributing them to lupus activity can result in overestimation of the prevalence of neuropsychiatric SLE and overtreatment of lupus, he said at the meeting.

The ACR case definitions have resulted in a great expansion of the perceived incidence and prevalence of neuropsychiatric lupus. But last year, a European League Against Rheumatism consensus statement on neuropsychiatric SLE suggested that the sweeping ACR conception goes too far, noted Dr. McCune, professor of internal medicine at the University of Michigan, Ann Arbor.

The EULAR report concluded that excluding headache, mood disorders, anxiety disorders, mild cognitive dysfunction, and polyneuropathy without electromyographic confirmation from the ACR list of manifestations of neuropsychiatric SLE would reduce the reported frequency of neuropsychiatric lupus by half while doubling the specificity of the ACR nomenclature from 46% to 93% (Ann. Rheum. Dis. 2010;69:2074-82).

The EULAR report identified three risk factors consistently associated with roughly a fivefold increased likelihood that a neuropsychiatric symptom is actually due to the patient’s lupus rather than to a secondary cause such as comorbid hypertension, infection, or cardiac vegetations. These risk factors are generalized SLE activity; a moderate to high titer of antiphospholipid antibodies, which particularly predispose to lupus as the primary cause in cases involving seizures, cerebrovascular disease, or chorea; and previous neuropsychiatric SLE manifestations, which greatly increase the likelihood that seizures or cognitive dysfunction in a lupus patient are actually due to the SLE.

Another key point made in the EULAR consensus statement was that 50%-60% of neuropsychiatric SLE events occur at the onset of lupus or within the first year afterward.

"That means one has to be alert to the possibility that someone who presents with an incompletely developed syndrome may ultimately turn out to have lupus," Dr. McCune observed.

The impact of the ACR’s broad list of manifestations of neuropsychiatric lupus was apparent in a recent meta-analysis of 10 studies of the prevalence of neuropsychiatric SLE conducted since the ACR report was published. The average prevalence of neuropsychiatric syndromes as defined by the ACR was 56% among lupus patients, and in two studies it exceeded 90%. The three most common neuropsychiatric syndromes in the meta-analysis were headache in 28% of SLE patients, mood disorders in 21%, and cognitive dysfunction in 20% (Semin. Arthritis Rheum. 2010 Oct. 20 [doi:10.1016/j.semarthrit.2010.08.001]).

Dr. McCune noted that when the Michigan Lupus Epidemiology and Surveillance Program (MiLES) was established close to a decade ago, investigators chose to track only a subset of the 19 neuropsychiatric syndromes on the ACR list: seizure disorders, cerebrovascular accidents, psychosis, mononeuropathy, aseptic meningitis, acute transverse myelitis, chorea, and cranial neuropathy.

MiLES is an ongoing Centers for Disease Control and Prevention–sponsored population-based survey of lupus in Wayne and Washtenaw counties. Together the two counties have a population of about 2.3 million that’s 55% white and 38% African American. To date, in an interim analysis, 2,372 residents have been identified who fulfill ACR requirements for the diagnosis of SLE. That’s an SLE prevalence of roughly 1 in 1,000 individuals, a considerably higher figure than the usually cited estimates of 1 in 500 among African American women and 1 per 2,000 white women, with much lower rates in men.

Among SLE patients identified in MiLES, 18% had at least one neuropsychiatric manifestation attributed by investigators to their lupus. Several intriguing sex-based differences have been found. For instance, the prevalence of neuropsychiatric SLE was significantly higher among men with SLE, at 26%, compared with 17.6% in women, even though men had a shorter average disease duration. This finding is consistent with the hypothesis that men tend to have more severe lupus even though they have a much lower incidence of the disease than women.

Seizures were the most common neuropsychiatric manifestation in both men and women with lupus, but were roughly twice as common among the men. Aseptic meningitis was also significantly more prevalent among male lupus patients.

African American women with SLE had significantly more seizures, cerebrovascular accidents, and psychosis than did white women. Among men, in contrast, there were no significant racial differences in any of the neurologic features being tracked, Dr. McCune said.

He said he had no relevant financial disclosures.

Stricter Definition of Neuropsychiatric Involvement in SLE Urged