Abstract
BACKGROUND: Neuropsychiatric symptoms in SLE and other systemic autoimmune rheumatic diseases (SARDs) are challenging to diagnose, attribute and manage. We investigated the timings of onset of a broad range of neuropsychiatric (NP) symptoms in relation to timing of SLE onset. In addition, we explored whether NP symptoms may be a prodrome to SARD onset and to subsequent flares. METHODS: We collected patient reports of the timing of their first episode of 29 NP symptoms relative to SLE non-NP symptom onset. Surveys (n = 676 SLE patients and n = 400 clinicians) and interviews (n = 50 clinicians; and n = 69 SARD patients, including 27 SLE patients) were completed from 2022 to 2023, and analysed using mixed methods. FINDINGS: The majority of NP symptoms did not first present around the time of SLE onset, contrary to the prevailing view among many rheumatology participants and in the literature. For example, among patients who experienced hallucinations, 54% reported first presentation >1 year after disease onset. Patient interviews also revealed that a range of NP symptoms may be a prodrome to SLE/SARDs onset and later flares, including symptoms not represented in existing classification criteria. Evidence of a possible prodromal syndrome was elicited from those patients who experienced hallucinations. Of these, 61% (SLE) and 34% (other SARDs) reported increasingly disrupted dreaming sleep (usually nightmares) prior to their hallucinations. In-depth interviews revealed that progression of symptoms in flares showed a high degree of inter-patient variation, whilst symptom progression was often similar in individual patient's recurrent flares. INTERPRETATION: Neuropsychiatric symptoms can first present at any stage in the SLE disease course. Attributional decisions should evaluate timings of NP symptoms in relation to timing of SLE/SARD symptom onset rather than time of diagnosis due to frequent diagnostic delays. Greater recognition of prodromal/early NP symptoms indicating impending SLE flares (and potentially other SARD flares) could enable quicker flare identification and treatment. FUNDING: The Lupus Trust.