Sern Chin LİM, Yusma Lyana Md YUSOF, Bushra JOHARİ, Roqiah Fatmawati Abdul KADİR, Swee Ping TANG

Neuropsychiatric lupus in Malaysian children: clinical characteristics, imaging features and 12-month outcomes

Background. Neuropsychiatric lupus (NPSLE) serves as a marker of severe disease in children with juvenile onset systemic lupus erythematosus (JSLE). This study aims to characterise the clinical and imaging features at diagnosis; and outcomes after 12 months in Malaysian children with NPSLE. Methods. A retrospective study of all NPSLE patients seen at the Pediatric Rheumatology Unit, Selayang Hospital from January 2004 to May 2017. Results. Twenty-eight (19.8%) of 141 JSLE patients had NPSLE with a median presenting age of 10 years (IQR 9 – 12), median follow-up of 7 years (IQR 4 – 11) and female: male ratio of 3.7:1. Twenty-three patients had single episodes of NPSLE and five patients had two distinct episodes each. The mean disease activity score (SLEDAI2K) was 24.9±11.8 at presentation with 81.8% having high disease activity (score >12). Majority (60.6%) present with NPSLE within the first year of SLE diagnosis whilst the remainder occurred at a median of five years (IQR 3-7) post-SLE diagnosis. Majority (75.8%) had central nervous system (CNS) involvement commonly presenting with seizures, delirium and visual complaints whilst 24.2% had peripheral nervous system (PNS) involvement. Frequent accompanying features included hypocomplementemia, acute cutaneous lupus and lupus nephritis. Autoantibodies were common; ANA (100%), anti-dsDNA (78.8%) anti-RNP (39.4%) and anti-Sm (39.4%). Abnormalities were seen in 85.7% of the magnetic resonance imaging (MRI) studies performed, predominantly supratentorial white matter hyperintensities on T2 images whilst cerebrospinal fluid examination was normal in the majority. All patients with CNS involvement received corticosteroids with immunosuppressive therapy: Cyclophosphamide (20), Rituximab (2). Treatment for PNS involvement included corticosteroids with Azathioprine (6) or Mycophenolate mofetil (2). At 12 months post-NPSLE, majority (85.7%) recovered without any neurological sequelae. Conclusions. Juvenile-onset NPSLE presents with a myriad of clinical features. It is associated with high disease activity and non-specific MRI features. With early diagnosis and treatment, the majority had good prognosis.

PDF

___

1. Smith PP, Gordon C. Systemic lupus erythematosus: clinical presentations. Autoimmun Rev 2010; 10: 43- 45.

2. Duarte-Delgado NP, Vásquez G, OrtizReyes BL. Blood-brain barrier disruption and neuroinflammation as pathophysiological mechanisms of the diffuse manifestations of neuropsychiatric systemic lupus erythematosus. Autoimmun Rev 2019; 18: 426-432.

3. Haji Muhammad Ismail Hussain I, Loh WF, Sofiah A. Childhood cerebral lupus in an Oriental population. Brain Dev 1999; 21: 229-235.

4. Yu HH, Lee JH, Wang LC, Yang YH, Chiang BL. Neuropsychiatric manifestations in pediatric systemic lupus erythematosus: a 20-year study. Lupus 2006; 15: 651-657.

5. Khajezadeh MA, Zamani G, Moazzami B, Nagahi Z, Mousavi-Torshizi M, Ziaee V. Neuropsychiatric involvement in juvenile-onset systemic lupus erythematosus. Neurol Res Int 2018; 2018: 2548142.

6. Kivity S, Agmon-Levin N, Zandman-Goddard G, Chapman J, Shoenfeld Y. Neuropsychiatric lupus: a mosaic of clinical presentations. BMC Med 2015; 13: 43.

7. Benseler SM, Silverman ED. Neuropsychiatric involvement in pediatric systemic lupus erythematosus. Lupus 2007; 16: 564-571.

8. Olfat MO, Al-Mayouf SM, Muzaffer MA. Pattern of neuropsychiatric manifestations and outcome in juvenile systemic lupus erythematosus. Clin Rheumatol 2004; 23: 395-399.

9. Sit JKK, Chan WKY. Risk factors for damage in childhood-onset systemic lupus erythematosus in Asians: a case control study. Pediatr Rheumatol Online J 2018; 16: 56.

10. Suwanpakdee P, Nabangchang C, Lumpaopong A. Neuropsychiatric manifestations in pediatric systemic lupus erythematosus. J Med Assoc Thai 2017; 100: 1196.

11. Petri M, Orbai AM, Alarcón GS, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 2012; 64: 2677-2686.

12. The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum 1999; 42: 599-608.

13. Gladman DD, Ibañez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. J Rheumatol 2002; 29: 288-291.

14. AlE’ed A, Vega-Fernandez P, Muscal E, et al; CARRA Neuropsychiatric Systemic Lupus Erythematosus Working Group. Challenges of diagnosing cognitive dysfunction with neuropsychiatric systemic lupus erythematosus in childhood. Arthritis CareRes (Hoboken) 2017; 69: 1449-1459.

15. Harel L, Sandborg C, Lee T, von Scheven E. Neuropsychiatric manifestations in pediatric systemic lupus erythematosus and association with antiphospholipid antibodies. J Rheumatol 2006; 33: 1873-1877.

16. de Amorim JC, Frittoli RB, Pereira D, et al. Epidemiology, characterization, and diagnosis of neuropsychiatric events in systemic lupus erythematosus. Expert Rev Clin Immunol 2019; 15: 407-416.

17. Demirkaya E, Bilginer Y, Aktay-Ayaz N, et al. Neuropsychiatric involvement in juvenile systemic lupus erythematosus. Turk J Pediatr 2008; 50: 126- 131.

18. Faria R, Gonçalves J, Dias R. Neuropsychiatric systemic lupus erythematosus involvement: towards a tailored approach to our patients? Rambam Maimonides Med J 2017; 8: e0001.

19. Bertsias GK, Boumpas DT. Pathogenesis, diagnosis and management of neuropsychiatric SLE manifestations. Nat Rev Rheumatol 2010; 6: 358-367.

20. Magro-Checa C, Zirkzee EJ, Huizinga TW, SteupBeekman GM. Management of neuropsychiatric systemic lupus erythematosus: current approaches and future perspectives. Drugs 2016; 76: 459-483.

21. Ho RC, Thiaghu C, Ong H, et al. A meta-analysis of serum and cerebrospinal fluid autoantibodies in neuropsychiatric systemic lupus erythematosus. Autoimmun Rev 2016; 15: 124-138.

22. Al-Obaidi M, Saunders D, Brown S, et al. Evaluation of magnetic resonance imaging abnormalities in juvenile onset neuropsychiatric systemic lupus erythematosus. Clin Rheumatol 2016; 35: 2449-2456.

23. Ainiala H, Dastidar P, Loukkola J, et al. Cerebral MRI abnormalities and their association with neuropsychiatric manifestations in SLE: a population‐based study. Scand J Rheumatol 2005; 34: 376-382.

24. Govoni M, Hanly JG. The management of neuropsychiatric lupus in the 21st century: still so many unmet needs? Rheumatology (Oxford) 2020; 59(Suppl5): v52-v62.

25. Lopes SRM, Gormezano NWS, Gomes RC, et al; Brazilian Childhood-onset Systemic Lupus Erythematosus Group. Outcomes of 847 childhoodonset systemic lupus erythematosus patients in three age groups. Lupus 2017; 26: 996-1001.

26. Mansour HE, Habeeb RA, El-Azizi NO, et al. Electroencephalography in systemic lupus erythematosus patients with neuropsychiatric manifestations. Egypt J Int Med 2020; 32: 11.

27. Bertsias GK, Ioannidis JPA, Aringer M, et al. EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations: report of a task force of the EULAR standing committee for clinical affairs. Ann Rheum Dis 2010; 69: 2074-2082.

28. Groot N, Shaikhani D, Teng YKO, et al. Longterm clinical outcomes in a cohort of adults with childhood-onset systemic lupus erythematosus. Arthritis Rheumatol 2019; 71: 290-301.