Neuropsychiatric symptoms in Systemic Lupus Erythematosus: mixed methods analysis of patient-derived attributional evidence in the international INSPIRE project

Melanie Sloan; Thomas A Pollak; Efthalia Massou; Guy Leschziner; Laura Andreoli; Rupert Harwood; Michael Bosley; Mervi Pitkanen; Wendy Diment; Alessandra Bortoluzzi; Michael S Zandi; Mandeep Ubhi; Caroline Gordon; David Jayne; Felix Naughton; Colette Barrere; Chris Wincup; James Brimicombe; James A Bourgeois; David D'Cruz

doi:10.1093/rheumatology/keae194

Neuropsychiatric symptoms in Systemic Lupus Erythematosus: mixed methods analysis of patient-derived attributional evidence in the international INSPIRE project

Rheumatology (Oxford). 2024 Mar 22:keae194. doi: 10.1093/rheumatology/keae194. Online ahead of print.

Authors

Melanie Sloan¹, Thomas A Pollak², Efthalia Massou¹, Guy Leschziner³, Laura Andreoli⁴, Rupert Harwood⁵, Michael Bosley⁶, Mervi Pitkanen², Wendy Diment⁶, Alessandra Bortoluzzi⁷, Michael S Zandi⁸, Mandeep Ubhi⁹, Caroline Gordon⁹, David Jayne¹⁰, Felix Naughton¹¹, Colette Barrere⁶, Chris Wincup¹², James Brimicombe¹, James A Bourgeois¹³, David D'Cruz¹⁴

Affiliations

¹ Department of Public Health and Primary Care Unit, University of Cambridge, UK.
² Institute of Psychiatry, Psychology and Neuroscience, King's College London, and South London and Maudsley NHS foundation trust, London, UK.
³ Department of Neurology, Guy's and St Thomas' Hospitals NHS Foundation Trust, London, UK.
⁴ Unit of Rheumatology and Clinical Immunology, ASST Spedali Civili, ; Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
⁵ Swansea University Medical School, Wales.
⁶ Patient and Public Co-Investigators.
⁷ Rheumatology Unit, Department of Medical Sciences, University of Ferrara and Azienda Ospedaliero-Universitaria S. Anna, Ferrara, Italy.
⁸ Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, London, UK.
⁹ Rheumatology Research Group, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
¹⁰ Department of Medicine, University of Cambridge, UK.
¹¹ Behavioural and Implementation Science Group, School of Health Sciences, University of East Anglia, Norwich, UK.
¹² Department of Rheumatology, Kings College Hospital London, UK.
¹³ Department of Psychiatry and Behavioral Sciences, University of California, Davis Medical Center, Sacramento, California, United States.
¹⁴ The Louise Coote Lupus Unit, Guy's and St Thomas' Hospitals NHS Foundation Trust, London, UK.

PMID: 38518094
DOI: 10.1093/rheumatology/keae194

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 contributes 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: 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 attributability of neuropsychiatric symptoms to the direct disease effects on the brain/nervous system.

Results: We recruited 2,817 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. Clinician and patients reported insufficient time to discuss patient-reported attributional evidence. Symptoms viewed as indirectly related/non-attributable were often less prioritised 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.

Keywords: CNS lupus; NPSLE; Neuropsychiatric lupus; SLE; attribution; autoimmunity; biopsychosocial; diagnosis; inflammatory arthritis; mental health; misattribution; patient-clinician interactions; rheumatology.