Treatment of neuropsychiatric systemic lupus erythematosus: clinical challenges and future perspectives

ABSTRACT

Introduction: Neuropsychiatric (NP) involvement represents an emerging frontier in systemic lupus erythematosus (SLE), posing significant challenges due to its clinical diversity and obscure pathophysiology. The authors herein discuss selected aspects in the management of NPSLE based on existing literature and our experience, aiming to facilitate routine medical care.

Areas covered: Research related to diagnosis, neuroimaging, treatment and outcome is discussed, focusing on data published in PubMed during the last 5 years. Selected translational studies of clinical relevance are included.

Expert opinion: Identification of NPSLE patients who may benefit from appropriate treatment can be facilitated by attribution algorithms. Immunosuppressants are typically indicated in recurrent seizures, optic neuritis, myelopathy, psychosis and peripheral nerve disease, although a low threshold is recommended for cerebrovascular disease and other NP manifestations, especially when SLE is active. With the exception of stroke with positive antiphospholipid antibodies, anti-coagulation is rarely indicated in other syndromes. Refractory NPSLE can be treated with rituximab, whereas the role of other biologics remains unknown. Advances in the fields of biomarkers, neuroimaging for brain structural, perfusion or functional abnormalities, and design of novel compounds targeting not only systemic autoimmunity but also inflammatory and regenerative pathways within the nervous system, hold promise for optimizing NPSLE management.

KEYWORDS:

• Autoantibodies
• biologics
• brain hypoperfusion
• cerebrovascular disease
• immunosuppressive agents
• neuronal damage

Article highlights

• Attribution algorithms can help to discriminate SLE-related versus -unrelated neuropsychiatric events.

• Determining the inflammatory or ischemic/thrombotic basis of NPSLE by considering the type of manifestation, the disease state, serological (e.g., antiphospholipid antibodies), and imaging findings, is critical to guide appropriate treatment.

• Cyclophosphamide in combination with glucocorticoids is recommended for active, severe inflammatory NPSLE.

• Rituximab can be used in refractory cases whereas the role of other biologics remains unknown.

• Besides novel anti-inflammatory agents, neuroprotective strategies are being explored in NPSLE.

• Research in the field of biomarkers and advanced neuroimaging modalities might further assist the diagnosis and treatment of patients with NPSLE.

Acknowledgments

Figure 2 is developed with the help of the Smart Servier Medical Art (https://smart.servier.com/).

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers in this manuscript have no relevant financial or other relationships to disclose.