Neuropsychiatric symptoms in systemic lupus erythematosus: mixed methods analysis of patient-derived attributional evidence in the international INSPIRE project

Abstract

Abstract Objective Attribution of neuropsychiatric symptoms in systemic lupus erythematosus (SLE) relies heavily on clinician assessment. Limited clinic time, variable knowledge and symptom under-reporting contribute to discordance between clinician assessments and patient symptoms. We obtained attributional data directly from patients and clinicians in order to estimate and compare potential levels of direct attribution to SLE of multiple neuropsychiatric symptoms using different patient-derived measures. Methods Quantitative and qualitative data analysed included: the prevalence and frequency of neuropsychiatric symptoms, response to corticosteroids and concurrence of neuropsychiatric symptoms with non-neuropsychiatric SLE disease activity. SLE patients were also compared with controls and inflammatory arthritis (IA) patients to explore the attributability of neuropsychiatric symptoms to the direct disease effects on the brain/nervous system. Results We recruited 2817 participants, including 400 clinicians. SLE patients (n = 609) reported significantly higher prevalences of neuropsychiatric symptoms than controls (n = 463) and IA patients (n = 489). SLE and IA patients’ quantitative data demonstrated multiple neuropsychiatric symptoms relapsing/remitting with other disease symptoms such as joint pain. Over 45% of SLE patients reported resolution/improvement of fatigue, positive sensory symptoms, severe headache, and cognitive dysfunction with corticosteroids. Evidence of direct attributability in SLE was highest for hallucinations and severe headache. SLE patients had greater reported improvement from corticosteroids (p= 0.008), and greater relapsing-remitting with disease activity (P < 0.001) in the comparisons with IA patients for severe headache. Clinicians and patients reported insufficient time to discuss patient-reported attributional evidence. Symptoms viewed as indirectly related/non-attributable were often less prioritized for discussion and treatment. Conclusion We found evidence indicating varying levels of direct attributability of both common and previously unexplored neuropsychiatric symptoms in SLE patients, with hallucinations and severe headache assessed as the most directly attributable. There may also be—currently under-estimated—direct effects on the nervous system in IA and other systemic rheumatological diseases.