Neuropsychiatric SLE Less Frequent Among Patients With Late- vs Early-Onset Lupus

Neuropsychiatric systemic lupus erythematosus (NPSLE) is less common among patients with late- vs early-onset lupus, though polypharmacy and increased incidence of neurological comorbidities may complicate diagnosis among those with late-onset lupus, according to results of a systematic review and meta-analysis published in Rheumatology.

Late-onset systemic lupus erythematosus (SLE) is associated with lower frequency of neuropsychiatric manifestations and lupus nephritis, which are often milder than in patients with early-onset.

Investigators aimed to assess differences in frequency and clinical manifestations of NPSLE among patients with late- (SLE diagnosis at age 50 or later) vs early-onset (SLE diagnosis before age 50) SLE.

Investigators searched the Cochrane Library, Web of Science, and PubMed databases from 1959 to 2022 for studies evaluating frequency of NPSLE that used a late-onset SLE group for comparison.  The early-onset group included patients with childhood-onset (diagnosed at <18 years of age) SLE. The primary endpoint was NPSLE manifestations.

A total of 44 studies (n=17,865 patients with early-onset SLE; n=2970 patients with late-onset SLE) were included in the analysis. Among these, 3326 patients had central nervous system involvement.

Investigators found patients with early-onset SLE had a higher frequency of cumulative NPSLE vs patients with late-onset (odds ratio [OR], 1.41; 95% CI, 1.24-1.59; P <.0001). Patients with early-onset SLE vs late-onset also had a higher frequency of seizures (OR, 1.68; 95% CI, 1.27-2.22; P =.0003) and psychosis (OR, 1.72; 95% CI, 1.23-2.41; P =.0014).

Patients with childhood-onset SLE were reported as a separate group in 15 studies. Subgroup analysis revealed NPSLE was more common among patients with childhood-onset SLE vs patients with late-onset (OR, 1.53; 95% CI, 1.16-2.01; P =.0025). No differences were noted when compared against patients with early-onset SLE.

Patients with late-onset SLE vs early-onset had a higher frequency of peripheral neuropathy (OR, 0.64; 95% CI, 0.47-0.86; P =.004). Patients with early-onset SLE vs late-onset had a significantly greater frequency of lupus nephritis (OR, 2.46; 95% CI, 2.23-2.71; P <.0001).

Frequency of NPSLE at time of initial presentation was reported in 13/44 studies and revealed patients with early-onset SLE vs late-onset had similar frequencies of NPSLE at initial diagnosis (OR, 1.19; 95% CI, 0.88-1.61; P =.51).

This analysis was limited by a lack of uniformity across all included studies in the neurologic attribution model used. Additionally, use of the American College of Rheumatology 1999 definition for NPSLE may have limited the scope of manifestations included.

The study authors concluded, “Further studies are needed to elucidate if these findings are due to attrition bias or represent a distinct clinical phenotype.”