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

Articles in Press

Document Type : Review Article

Authors

1 Ziauddin Medical College, Ziauddin University, Karachi, Pakistan

2 Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan

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.

Keywords

Main Subjects

References
  1. Cullinane PW, Carr AS, Irani SR, Warner TT. Stiff person syndrome. In: Hanna MG, editor. Handbook of Clinical Neurology. 203. Amsterdam, Netherlands: Elsevier; 2024. p. 211-33.
  2. Matsui N, Tanaka K, Ishida M, Yamamoto Y, Matsubara Y, Saika R, et al. Prevalence, Clinical Profiles, and Prognosis of Stiff-Person Syndrome in a Japanese Nationwide Survey. Neurol Neuroimmunol Neuroinflamm 2023; 10(6): e200165.
  3. Yu H, Nagafuchi Y, Fujio K. Clinical and Immunological Biomarkers for Systemic Lupus Erythematosus. Biomolecules 2021; 11(7): 928.
  4. Gómez-Bañuelos E, Fava A, Andrade F. An update on autoantibodies in systemic lupus erythematosus. Curr Opin Rheumatol 2023; 35(2): 61-7.
  5. Ameer MA, Chaudhry H, Mushtaq J, Khan OS, Babar M, Hashim T, et al. An Overview of Systemic Lupus Erythematosus (SLE) Pathogenesis, Classification, and Management. Cureus 2022; 14(10): e30330.
  6. Goëb V, Dubreuil F, Cabre P, Jean-Baptiste G, Arfi S. Lupus revealing itself after a stiff-person syndrome. Lupus 2004; 13(3): 215.
  7. Akhil A, Bansal R, Anupam K, Tandon A, Bhatnagar A. Systemic lupus erythematosus: latest insight into etiopathogenesis. Rheumatol Int 2023; 43(8): 1381-93.
  8. Dade M, Berzero G, Izquierdo C, Giry M, Benazra M, Delattre JY, et al. Neurological Syndromes Associated with Anti-GAD Antibodies. Int J Mol Sci 2020; 21(10): 3701.
  9. Baizabal-Carvallo JF, Jankovic J. Autoimmune and paraneoplastic movement disorders: An update. J Neurol Sci 2018; 385: 175-84.
  10. Ota Y, Srinivasan A, Capizzano AA, Bapuraj JR, Kim J, Kurokawa R, et al. Central Nervous System Systemic Lupus Erythematosus: Pathophysiologic, Clinical, and Imaging Features. Radiographics 2022; 42(1): 212-32.
  11. Matsui N, Tanaka K, Izumi Y. [Stiff-Person Syndrome]. Brain Nerve 2023; 75(6): 749-54.
  12. Rakocevic G, Alexopoulos H, Dalakas MC. Quantitative clinical and autoimmune assessments in stiff person syndrome: evidence for a progressive disorder. BMC Neurol 2019; 19(1): 1.
  13. van Vugt RM, Derksen RH, Kater L, Bijlsma JW. Deforming arthropathy or lupus and rhupus hands in systemic lupus erythematosus. Ann Rheum Dis 1998; 57(9): 540-4.
  14. Pretorius E, Struwig W. Stiff person syndrome (SPS): Literature review and case report. S Afr J Psychiatry 2013; 19(4): 228-31.
  15. El-Abassi R, Soliman MY, Villemarette-Pittman N, England JD. SPS: Understanding the complexity. J Neurol Sci 2019; 404: 137-49.
  16. Dalakas MC. Stiff person syndrome: advances in pathogenesis and therapeutic interventions. Curr Treat Options Neurol 2009; 11(2): 102-10.
  17. Muranova A, Shanina E. Stiff Person Syndrome. [Cited: 2023 Jul 10]. In: StatPearls [Online]. Treasure Island, FL: StatPearls Publishing; 2026. PMID: 34424651.
  18. Aringer M, Costenbader K, Daikh D, Brinks R, Mosca M, Ramsey-Goldman R, et al. 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus. Arthritis Rheumatol 2019; 71(9): 1400-12.
  19. Vasquez-Canizares N, Wahezi D, Putterman C. Diagnostic and prognostic tests in systemic lupus erythematosus. Best Pract Res Clin Rheumatol 2017; 31(3): 351-63.
  20. Dubai FM, Isa A. Overlap Syndrome in a Male Presenting With Progressive Lower Limb Weakness: A Case Report. Cureus 2023; 15(1): e33664.
  21. Dalakas MC, Fujii M, Li M, McElroy B. The clinical spectrum of anti-GAD antibody-positive patients with stiff-person syndrome. Neurology 2000; 55(10): 1531-5.
  22. Ortiz JF, Ghani MR, Morillo Cox Á, Tambo W, Bashir F, Wirth M, et al. Stiff-Person Syndrome: A Treatment Update and New Directions. Cureus 2020; 12(12): e11995.
  23. Newton JC, Harned ME, Sloan PA, Salles SS. Trialing of intrathecal baclofen therapy for refractory stiff-person syndrome. Reg Anesth Pain Med 2013; 38(3): 248-50.
  24. Rakocevic G, Floeter MK. Autoimmune stiff person syndrome and related myelopathies: understanding of electrophysiological and immunological processes. Muscle Nerve 2012; 45(5): 623-34.
  25. Bhatti AB, Gazali ZA. Recent Advances and Review on Treatment of Stiff Person Syndrome in Adults and Pediatric Patients. Cureus 2015; 7(12): e427.
  26. Dalakas MC. Advances in the pathogenesis and treatment of patients with stiff person syndrome. Curr Neurol Neurosci Rep 2008; 8(1): 48-55.
  27. Esch ME, Newsome SD. Improvement of stiff-person syndrome symptoms in pregnancy: Case series and literature review. Neurol Neuroimmunol Neuroinflamm 2020; 7(3): e684.
  28. Katarzyna PB, Wiktor S, Ewa D, Piotr L. Current treatment of systemic lupus erythematosus: a clinician's perspective. Rheumatol Int 2023; 43(8): 1395-407.
  29. Fava A, Petri M. Systemic lupus erythematosus: Diagnosis and clinical management. J Autoimmun 2019; 96: 1-13.
  30. Luo SF, Kuo CF. Comorbidities in patients with systemic lupus erythematosus prior to and following diagnosis: case-control study. Lupus Sci Med 2017; 4(Suppl 1): A80-1.
  31. Caffrey D, Finn CT, Song SM, Burton F, 3rd, Arsan C. Stiff-Person Syndrome and Psychiatric Comorbidities: A Systematic Review. J Acad Consult Liaison Psychiatry 2021; 62(1): 3-13.
  32. Gerschlager W, Schrag A, Brown P. Quality of life in stiff-person syndrome. Mov Disord 2002; 17(5): 1064-7.
  33. Olesińska M, Saletra A. Quality of life in systemic lupus erythematosus and its measurement. Reumatologia 2018; 56(1): 45-54.
  34. Kundnani NR, Levai MC, Popa MD, Borza C, Iacob M, Mederle AL, et al. Biologics in Systemic Lupus Erythematosus: Recent Evolutions and Benefits. Pharmaceutics 2024; 16(9): 1176.
  35. Athanassiou P, Athanassiou L. Current Treatment Approach, Emerging Therapies and New Horizons in Systemic Lupus Erythematosus. Life (Basel) 2023; 13(7): 1496.
  36. Morand EF, Fernandez-Ruiz R, Blazer A, Niewold TB. Advances in the management of systemic lupus erythematosus. BMJ 2023; 383: e073980.
  37. Kyverna Therapeutics. Kyverna’s KYV-101 Receives U.S. FDA IND Clearance for Treatment of Patients With Treatment-Refractory Stiff-Person Syndrome in the KYSA-8 Phase 2 Trial [Online]. [Cited 2024 Jun 20]. Available From: URL: https://ir.kyvernatx.com/news-releases/news-release-details/kyvernas-kyv-101-receives-us-fda-ind-clearance-treatment
  38. Luo S, Long H, Lu Q. Recent advances in understanding pathogenesis and therapeutic strategies of Systemic Lupus Erythematosus. Int Immunopharmacol 2020; 89(Pt A): 107028.
  39. Lee L, Werth V. Lupus Erythematosus. In: Bolognia JL, Jorizzo JL, Schaffer JV. Dermatology. 3rd ed. London, UK: Elsevier Ltd; 2012.
  40. Tench CM, McCurdie I, White PD, D'Cruz DP. The prevalence and associations of fatigue in systemic lupus erythematosus. Rheumatology (Oxford) 2000; 39(11): 1249-54.
  41. Yazdany J, Yelin E. Health-related quality of life and employment among persons with systemic lupus erythematosus. Rheum Dis Clin North Am 2010; 36(1): 15-32, vii.
  42. Apollo Hospitals. The Importance of Early Diagnosis and Treatment for Neurological Disorders [Online]. [Cited: 2025 Feb 18]. Available from: URL: https://www.apollohospitals.com/health-library/the-importance-of-early-diagnosis-and-treatment-for-neurological-disorders.
  43. Munhoz RP, Fameli H, Teive HA. Stiff person syndrome as the initial manifestation of systemic lupus erythematosus. Mov Disord 2010; 25(4): 516-7.
  44. Atlanta Neuroscience Institute. The Importance Of Early Detection In Neurological Disorders [Online]. Available from: URL: https://atlneuroinstitute.org/the-importance-of-early-detection-in-neurological-disorders/.
  45. Lavorgna L, Brigo F, Esposito S, Abbadessa G, Sparaco M, Lanzillo R, et al. Public Engagement and Neurology: An Update. Brain Sci 2021; 11(4): 429.
  46. Barber MRW, Drenkard C, Falasinnu T, Hoi A, Mak A, Kow NY, et al. Global epidemiology of systemic lupus erythematosus. Nat Rev Rheumatol 2021; 17(9): 515-32.
  47. Fortuna G, Brennan MT. Systemic lupus erythematosus: epidemiology, pathophysiology, manifestations, and management. Dent Clin North Am 2013; 57(4): 631-55.
  48. Etemadifar M, Aghababaei A, Nouri H, Kargaran PK, Mohammadi S, Salari M. Autoimmune encephalitis: the first observational study from Iran. Neurol Sci 2022; 43(2): 1239-48.
Current Journal of Neurology

Articles in Press, Accepted Manuscript
Available Online from 29 July 2026
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