Stiff-person syndrome and systemic lupus erythematosus: A cross-disease examination of autoimmunity and neurological involvement

Abstract

Background: Stiff-person syndrome (SPS) is a rare autoimmune neurological disorder characterized by progressive muscle rigidity and spasms, while systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disease. Despite having different clinical presentations, both conditions share underlying immunological mechanisms including antibody production, B-cell dysfunction, and cytokine dysregulation. The rare co-occurrence of SPS and SLE is explored in this review, analyzing shared pathophysiology, overlapping neurological features, diagnostic challenges, and therapeutic implications.

Methods: A comprehensive literature search was conducted in PubMed, Scopus, and Cochrane up to June 2025 using the keywords “stiff person syndrome”, “systemic lupus erythematosus”, “autoimmune overlap”, and “case report” in various combinations. Additional sources were identified through manually screening the relevant articles. Inclusion criteria were articles describing SPS, SLE, or their overlap, including case reports, case series, retrospective studies, and reviews. Extrusion criteria were conference abstracts without full texts and studies not directly addressing SPS and SLE. In total, 120 publications were screened, of which 53 met the inclusion criteria and were analyzed in detail.

Results: A total of 53 studies were included, comprising case reports, case series, and reviews. These reports suggested a rare but clinical overlap between SPS and SLE.

The main themes identified were shared autoimmune mechanism, overlapping clinical manifestations, diagnostic challenges, and implications for therapy, underscoring the need for improved recognition and management.

Conclusion: Early diagnosis and an interdisciplinary approach are crucial for optimal outcomes. Improving the prognosis for individuals with overlapping autoimmune disorders requires increased awareness, integrated care approaches, and further research into common biomarkers and treatments.