The management of neuropsychiatric lupus in the 21st century: still so many unmet needs?

Abstract

Neuropsychiatric (NP) events occur in the majority of patients with SLE and predominantly affect the CNS in addition to the peripheral and autonomic systems. Approximately 30% of all NP events are attributable to SLE (NPSLE) and present most frequently around the time of SLE onset. NPSLE is associated with increased morbidity and mortality and the proposed pathogenesis includes both ischaemic and neuroinflammatory mechanisms. Following diagnosis and causal attribution, the treatment of NPSLE is tailored to the type of NP event, the predominant putative pathogenic pathway and the activity and severity of the clinical event. There is a dearth of controlled clinical trials to guide management, but therapeutic options include symptomatic, antithrombotic and immunosuppressive agents that are supported by observational cohort studies. Our objective was to review what is currently known about NPSLE and to identify deficiencies in diagnostic biomarkers, novel therapies and clinical trials for this manifestation of SLE.

Keywords: SLE; biomarkers; clinical trials; neuroimaging; neuropsychiatric; pathogenesis.

Fig. 1

Two autoimmune pathogenic pathways for NPSLE Ischaemic injury involving both large- and small-calibre vessels mediated by aPL antibodies, immune complexes and complement activation. Injury due to inflammation in which enhanced permeability of the BBB in association with antineuronal antibodies and formation of immune complexes lead to production of pro-inflammatory mediators and microglial activation. Both pathways may result in either focal or diffuse NP manifestations for which other non-SLE causes must be considered. pDC: plasmacytoid dendritic cell; dys: dysfunction.