Neuropsychiatric systemic lupus erythematosus: pathophysiology and the future of treatment

Systemic lupus erythematosus Systemic lupus erythematosus (SLE) is characterized by the presence of several autoantibodies, including anti-dsDNA antibodies [1,2]. Patients with SLE are affected with the following conditions: skin rash, arthritis, serositis, such as pericarditis and pleurisy, cytopenia, nephritis and neuropsychiatric (NP) symptoms. The prevalence of SLE ranges from 20 to 200 cases per 100,000 people worldwide, and the frequency appears to be increasing as SLE becomes more readily recognized and the survival rate increases [1,3]. Females between the ages of 15 and 50 years frequently suffer from SLE. Genetic, environmental, hormonal and epigenetic factors are involved in the onset of SLE. These factors cause the generation and activation of autoreactive T, B and plasma cells [4]. These cells cause inflammation and injury of several organs through cytokines, antibodies, immune complexes and the infiltration of cytotoxic cells. Thus, the current treatment strategy for SLE is primarily the regulation of exacerbated autoimmunity using immunosuppressive therapy. Recently, biological targeting B-cell therapies, including rituximab (anti-CD20), epratuzumab (anti-CD22) and belimumab (anti-B-cell activating factor), have been developed for patients with SLE. The development of immunosuppressive therapy has improved the prognosis for patients with SLE compared with previous treatments during the last decade. However, the 10-year survival rate is approximately 70–80% lower in patients with lupus nephritis or NP complications compared with patients without those complications [5]. Moreover, regardless of these treatments, refractory or relapsing cases are occasionally (30–40%) found in NP-SLE, which is defined not as a type of SLE, but as a list of disparate NP manifestations of SLE. As NP-SLE contributes to the morbidity and mortality of patients with SLE, it is important for clinicians to manage NP-SLE appropriately and specifically. Here, we describe the pathophysiology of NP-SLE and discuss future treatments of patients with NP-SLE, with reference to recently published reports.