Neuropsychiatric manifestations in early vs late-onset SLE: A systematic review and meta-analysis

Systemic lupus erythematosus (SLE) is more common in women of childbearing age, while late-onset SLE (ltSLE) is more prevalent among males. In older patients, the diagnosis of neuropsychiatric SLE is challenging due to polypharmacy and multiple comorbid conditions affecting the central nervous system.

Some models have been developed previously for the attribution of neurological symptoms to SLE; however, they lack specificity to ltSLE patients. Pamuk et al.¹ recently conducted a systematic literature review and meta-analysis, published in Rheumatology, to evaluate the frequency and specific clinical manifestations of neuropsychiatric systemic lupus erythematosus (NPSLE) in older patients with SLE. Here, we summarize the key points below.

Methods

• A literature search was conducted in PubMed, Web of Science, and Cochrane Library databases to identify relevant studies published between 1959–2022.
• A forest plot was used to compare odds ratios of NPSLE incidence and manifestations across age groups. Pearson’s correlation test was used to determine associations between the presence of autoantibodies and clinical manifestations.
• The SLE cohorts were categorized as:
  • Early-onset SLE (eSLE): SLE diagnosed at <50 years of age
    • Childhood-onset SLE: SLE diagnosed at <18 years of age
  • LtSLE: SLE diagnosed at ≥50 years of age

Key findings

• Out of 2,438 search results, 44 studies met the eligibility criteria, involving a total of 17,865 eSLE and 2,970 ltSLE patients. Central nervous system involvement was identified in 3,326 patients (2,955 eSLE and 371 ltSLE).
• Compared with the ltSLE group, the eSLE cohort had a significantly higher frequency of cumulative NPSLE, seizures, psychosis, lupus nephritis, anti-dsDNA, anti-Sm, anti-SS-A, and hypocomplementaemia. However, peripheral neuropathy was more common in the ltSLE group (Figure 1).
• The frequency of NPSLE did not differ between the eSLE and ltSLE groups at the time of initial diagnosis of SLE (Figure 1).
• In the eSLE group, the frequency of antiphospholipid syndrome was negatively associated with peripheral neuropathy (r = –0.84, p = 0.017). The presence of lupus nephritis was associated with hypocomplementaemia (r = 0.55, p = 0.015); however, there was no association between autoantibodies, hypocomplementaemia, and the clinical manifestations of NPSLE in either group.
• NPSLE was more frequent in childhood-onset SLE patients compared with the ltSLE group (odds ratio [OR], 1.53, 95% confidence interval [CI], 1.16–2.01; p = 0.0025), but did not differ significantly compared with the eSLE group (OR, 0.97; 95% CI, 0.82–1.16; p = 0.74).

Anti-dsDNA, anti-double-stranded deoxyribonucleic acid; Anti-Sm, anti-Smith; Anti-SS-A, Anti-Sjogren's Syndrome; CI, confidence interval; eSLE, early-onset systemic lupus erythematosus; LN, lupus nephritis; ltSLE, late-onset systemic lupus erythematosus; NPSLE, neuropsychiatric systemic lupus erythematosus; PNP, peripheral neuropathy; OR, odds ratio; SLE, systemic lupus erythematosus.
*Data from Pamuk, et al.¹

Key learnings

The frequency of NPSLE did not differ between the eSLE and ltSLE groups at the time of SLE diagnosis. The frequencies of neuropsychiatric manifestations were lower in ltSLE patients than in eSLE patients, suggesting that eSLE patients may be at an increased risk of NPSLE over time. The higher occurrence of peripheral neuropathy in the ltSLE group warrants further studies to determine whether these findings stem from attrition bias or indicate a distinct clinical phenotype. Further, an attribution model specific for the ltSLE group needs to be developed.