Clinical features and pathogenesis of Sjogrens disease related peripheral neuropathy and their relevance to clinical trials

Abstract Sjögren disease (SjD) is a chronic systemic autoimmune disorder characterized by immune-mediated destruction of moisture-producing glands (e.g. tears/saliva), leading to dryness. It also affects organs outside the glands, reflecting its systemic nature. Neurologic involvement is a common complication of SjD that can occur in up to 20% of SjD patients. Neurological manifestations in SjD span the central, peripheral, and autonomic systems, with the highest incidence of involvement occurring within the peripheral nervous system (PNS). The heterogeneity of neurologic manifestations in SjD complicates the diagnosis and treatment, which should be directed toward the underlying neuropathologic mechanism which is often unclear. Optimizing the diagnosis, evaluation, and management of these manifestations is essential to prevent severe disability and to design more effective clinical trials. In this review, we summarize the current understanding of SjD-related peripheral neuropathies. By detailing their specific pathogenetic mechanisms, we advocate for a targeted diagnostic and therapeutic framework designed to improve long-term patient outcomes.