LAUSR

SS is usually described as having severe fatigue, dryness, diffuse pain, glandular swelling, and various extraglandular (systemic) manifestations. Clinical trials have generally failed because the vast majority of enrolled patients had no extraglandular manifestations at the time of enrolment but suffered from fatigue, dryness and pain that did not significantly respond to the study medication. A number of hypotheses on the pathogenesis of pSS have been put forward, including disturbances of innate and adaptive immunity as well as abnormalities of the interface between immune disorders and the neuro-endocrine system related to lacrimal and secretory gland dysfunction. Thus, future therapies must be designed for improvement of the symptoms of dry eyes and dry mouth, extraglandular disease, and fatigue and cognitive deficits. Given the inadequacies and limitations of current treatment options, we suggest that innovative directions involving interactions with neuroscientists and neuropsychiatrists together or combined with new immune targeting may be hold promise for better treating pSS.