Clinical and laboratory manifestations of systemic lupus erythematosus in patients with neuropsychiatric disorders (eurasian renaissance register)

Objective: to investigate the clinical and laboratory manifestations of systemic lupus erythematosus (SLE) with nervous system lesions in a Kyrgyz cohort.

Subjects and methods. The prospective study enrolled 460 patients with SLE who fulfilled American College of Rheumatology (ACR) 1987 and SLICC 2012 criteria, and had been followed up at Academician M. Mirrahimov National  Center for Cardiology and Therapy, from January 2012 to December  2017 according to the Eurasian RENAISSANCE Register program. The 1999 ACR classification criteria were used to evaluate the neuropsychiatric manifestations of SLE (NPSLE). A psychiatrist diagnosed neuropsychiatric disorders according to the ICD-10. A psychologist identified cognitive impairment, by using the specific Mini-Mental State Examination (MMSE)  (a minischeme for examining a patient's mental status).

Results and discussion. Various NPSLEs  were detected  in 103 (22.39%) of the 460 patients.  According to the 1999 ACR criteria, 103 patients were diagnosed as having 155 different NPSLEs,  including 123 (79.35%) patients who had central nervous system (CNS)  disorders and 32 (20.65%) with peripheral  nervous system (PNS) damages. There were 76 (61.79%) focal 47 (38.21%) diffuse CNS disorders. Most patients with diffuse NPSLEs  were observed to have psychosis, the main manifestations  of which were visual and auditory hallucinations (72.34%). The patients with focal NPSLEs  had cerebrovascular disease (43.42%) with increase of level of antinuclear  antibodies,  antibodies against double-stranded DNA and hypocomplementemia (95.56, 86.52, and 73.85%, respectively). Patients  with CNS lesions were significantly more likely than those with PNS to have lupus nephritis and hematological  disorders (leukopenia,  lymphopenia, and thrombocytopenia), as well as high immunological  activity.

Conclusion. Most patients with diffuse NPSLEs were observed to have psychosis with visual and auditory hallucinations  (72.34%), and those with focal NPSLEs had cerebrovascular disease (43.42%) with a high frequency of immunological disorders. Lupus nephritis and hematological disorders with high immunological activity were significantly more common  in patients with CNS lesions than in those with PNS ones.

1. Nasonov EL. Klinicheskie rekomendatsii po revmatologii [Clinical recommendations for rheumatology]. 2nd ed. Moscow: GEOTAR-Media; 2010. P. 429-81 (In Russ.).

2. Vivaldo JF, de Amorim JC, Julio PR, et al. Definition of NPSLE: Does the ACR Nomenclature Still Hold? Front Med (Lausanne). 2018 May;31(5):138. doi: 10.3389/fmed.2018.00138. eCollection 2018.

3. Ivanova MM, Bliznyuk OI, Todau FI, Tumanova AA. Damage to the central nervous system in systemic lupus erythematosus. Klinicheskaya Meditsina. 1989;(2):93-7 (In Russ.).

4. Hanly JG, Urowitz MB, Sanchez-Guerrero J, et al. Neuropsychiatric events at the time of diagnosis of systemic lupus erythematosus: an international inception cohort study. Arthritis Rheum. 2007;56(1):265-73. doi: 10.1002/art.22305

5. Kivity S, Agmon-Levin N, Zandman-Goddard G, et al. Neuropsychiatric lupus: a mosaic of clinical presentations. BMC Medicine. 2015;13:48. doi: 10.1186/s12916-015-0269-9

6. The American of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum. 1999;42:599-608. doi: 10.1002/1529-0131(199904)42:4<599::AID-ANR2>3.0.CO;2-F

7. Ivanova MM, Bliznyuk OI, Shchekut'ev GA, Pushkova OV. Diagnosis of central nervous system damage in patients with systemic lupus erythematosus. Klinicheskaya Revmatologiya. 1991;(4):6-8 (In Russ.).

8. Zirkzee EJ, Steup-Beekman GM, van der Mast RC, et al. Prospective study of clinical phenotypes in neuropsychiatric systemic lupus erythematosus; multidisciplinary approach to diagnosis and therapy. J Rheumatol. 2012;39(11):2118-26. doi: 10.3899/jrheum.120545

9. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40(9):1725. doi: 10.1002/art.1780400928

10. Petri M, Orbai A, Alarson G, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics Classification Criteria for Systemic lupus erythematosus. Arthritis Rheum. 2012;64(8):2677-86. doi: 10.1002/art.34473

11. Gladman DD, Ibanez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. J Rheumatol. 2002;29:288-91.

12. Тареева ИЕ, Янушкевич ТН. Волчаночный нефрит у мужчин и женщин. Ревматология. 1985;(2):14-6 [Tareeva IE, Yanushkevich TN. Lupus nephritis in men and women. Revmatologiya. 1985;(2):14-6 (In Russ.)].

13. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2013;3 Suppl:1-150.

14. Zhang X. A study of effects of estrogen receptor and contrasupressor T cell subtype in pathogenesis of SLE. Rev Esp Rheum. 1993;20:420.

15. Magro-Checa C, Zirkzee EJ, Huizinga TW, et al. Management of neuropsychiatric systemic lupus erythematosus: current approaches and future perspectives. Drugs. 2016;76:459-83. doi: 10.1007/s40265-015-0534-3

16. Hanly JG, Urowitz MB, Sanchez-Guerrero J, et al. Systemic Lupus International Collaborating Clinics. Neuropsychiatric events at the time of diagnosis of systemic lupus erythematosus: An international inception cohort study. Arthritis Rheum. 2007;56(1):265-73. doi: 10.1002/art.22305

17. Everett CM, Graves TD, Lad S, et al. Aggressive CNS lupus vasculitis in the absence of systemic disease activity. Rheumatology (Oxford). 2008;47:107-9. doi: 10.1093/rheumatology/kem264

18. Johnson RT, Richardson EP. The neurological manifestations of systemic lupus erythematosus. Medicine (Baltimore). 1968;47:337-69. doi: 10.1097/00005792-196807000-00002

19. Kleinig TJ, Koszyca B. Fulminant leucocytoclastic brainstem vasculitis in a patient with otherwise indolent systemic lupus erythematosus. Lupus. 2009;18:486-90. doi: 10.1177/0961203308101548

20. Rizos T, Siegelin M, Hä hnel S, et al. Fulminant onset of cerebral immunocomplex vasculitis as first manifestation of neuropsychiatric systemic lupus erythematosus (NPSLE). Lupus. 2009;18:361-3. doi: 10.1177/0961203308097448

21. Rowshani AT, Remans P, Rozemuller A, Tak PP. Cerebral vasculitis as a primary manifestation of systemic lupus erythematosus. Ann Rheum Dis. 2005;64:784-6. doi: 10.1136/ard.2004.026542

22. Gerli R, Caponi L, Tincani A, et al. Clinical and serological associations of ribosomal P autoantibodies in systemic lupus erythematosus: Prospective evaluation in a large cohort of Italian patients. Rheumatology. 2002;41:1357-66. doi: 10.1093/rheumatology/41.12.1357

23. Hermosillo-Romo D, Brey RL. Diagnosis and management of patients with neuropsychiatric systemic lupus erythematosus (NPSLE). Best Pract Res Clin Rheumatol. 2002;16(2):229-44. doi: 10.1053/berh.2001.0223

24. Purandare KN, Wagle AC, Parker SR. Psychiatric morbidity in patients with systemic lupus erythematosus. Q J Med. 1999;92:283-6. doi: 10.1093/qjmed/92.5.283

25. Kakati S, Barman B, Ahmed SU, Hussain M. Neurological manifestations in systemic lupus erythematosus: A Single Centre Study from North East India. J Clin Diagn Res Int Med Sect 2017;11(01):OC05-OC09. doi: 10.7860/JCDR/2017/23773.9280

26. Khajezadeh MA, Zamani G, Moazzami B, et al. Neuropsychiatric involvement in juvenile-onset systemic lupus erythematosus. Neurol Res Int. 2018 May 29;2548142. doi: 10.1155/2018/2548142

27. Szmyrka M, Pokryszko-Dragan A, Slotwinski K, et al. Cognitive impairment, event-related potentials and immunological status in patients with systemic lupus erythematosus. Adv Clin Exp Med. 2018 Jul 2. doi: 10.17219/acem/76711

28. Brey RL, Holliday SL, Saklad AR, et al. Neuropsychiatric syndromes in lupus. Neurology. 2002;58:1214-20. doi: 10.1212/WNL.58.8.1214

29. Mikdashi J, Handwerger B. Predictors of neuropsychiatric damage systemic lupus erythematosus: data from the Maryland lupus cohort. J Rheumatol. 2004;43:1555-60. doi: 10.1093/rheumatology/keh384

30. Mok CC, Mak A, Chu WP, et al. Long-term survival of southern Chinese patients with systemic lupus erythematosus: a prospective study of all age-groups. Medicine (Baltimore). 2005;84:218-24. doi: 10.1097/01.md.0000170022.44998.d1

31. Whitelaw DA, Spangenberg JJ, Rickman R, et al. Association between the antiphospholipid antibody syndrome and neuropsychological impairment in SLE. Lupus. 1999;8:444-8. doi: 10.1177/096120339900800606

32. Lukjanowcz M, Brzosko M. Myelitis in the course of systemic lupus erythematosus. Polskie Arch Med Wew. 2009;119(1-2):67-72. doi: 10.20452/pamw.608

33. Krishnan C, Kaplin AI, Deshpande DM, et al. Transverse myelitis: pathogenesis, diagnosis and treatment. Front Biosci. 2004;9:1483-99. doi: 10.2741/1351

34. Toledano P, Orueta R, Rodriguez-Pinto I, et al. Peripheral nervous system involvement in systemic lupus erythematosus: Prevalence, clinical and immunological characteristics, treatment and out-come of a large cohort from a single centre. Autoimmun Rev. 2017 Jul;16(7):750-5. doi: 10.1016/j.autrev.2017.05.011

35. Saigal R, Bhargav R, Goyal L, et al. Peripheral neuropathy in systemic lupus erythematosus: Clinical and electrophysiological properties and their association with disease activity parameters. J Assoc Phys India. 2015 Dec;63(12):15-9.

36. Huynh C, Ho SL, Fong KY, et al. Peripheral neuropathy in systemic lupus erythematosus. J Clin Neurophysiol. 1999;16(2):164-8. doi: 10.1097/00004691-199903000-00010

37. Laysek RP, Levinson AI. Nevropatii pri zabolevaniyakh soedinitel'noy tkani. Zabolevaniya perifericheskoy nervnoy sistemy [Neuropathy in connective tissue diseases. Peripheral Nervous System Diseases]. Moscow: Meditsina; 1987. 280 p. (In Russ.).

38. Mondelli M, Romano C, Porta P, Rossi A. Electrophysiological evidence of «nerve entrapment syndromes» and subclinical peripheral neuropathy in progressive systemic sclerosis. J Neurol. 1995;242:185-94. doi: 10.1007/BF00919590