Treatment of Neuropsychiatric Systemic Lupus Erythematosus

Chapter

Abstract

Systemic lupus erythematosus includes a wide range of neuropsychiatric manifestations, in which various autoantibodies and cytokines could play a pathophysiologic role. The key drugs used in the treatment of neuropsychiatric systemic lupus erythematosus include corticosteroids and immunosuppressive agents to suppress the underlying inflammatory pathology, antiplatelet and antithrombotic agents in the context of thrombosis mediated by antiphospholipid antibodies, and agents for symptomatic treatment of individual neuropsychiatric manifestations, such as antiepileptic drugs for seizures and antipsychotic drugs for lupus psychosis.

Keywords

Treatment Corticosteroids Cyclophosphamide Antiplatelet and anticoagulant drugs Symptomatic treatment 

References

  1. 1.
    ACR Ad Hoc Committee on Neuropsychiatric Lupus Nomenclature. The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum. 1999;42:599–608.CrossRefGoogle Scholar
  2. 2.
    Matus S, et al. Antiribosomal-P autoantibodies from psychiatric lupus target a novel neuronal surface protein causing calcium influx and apoptosis. J Exp Med. 2007;204:3221–34.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Shiozawa S, et al. Interferon-alpha in lupus psychosis. Arthritis Rheum. 1992;35:417–22.CrossRefPubMedGoogle Scholar
  4. 4.
    Hirohata S, et al. Accuracy of cerebrospinal fluid IL-6 testing for diagnosis of lupus psychosis. A multicenter retrospective study. Clin Rheumatol. 2009;28:1319–23.CrossRefPubMedGoogle Scholar
  5. 5.
    Yoshio T, et al. IL-6, IL-8, IP-10, MCP-1 and G-CSF are significantly increased in cerebrospinal fluid but not in sera of patients with central neuropsychiatric lupus erythematosus. Lupus. 2016;25:997–1003.CrossRefPubMedGoogle Scholar
  6. 6.
    Bertsias GK, 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;69:2074–82.CrossRefPubMedGoogle Scholar
  7. 7.
    Magro-Checa C, et al. Management of neuropsychiatric systemic lupus erythematosus: current approaches and future perspectives. Drugs. 2016;76:459–83.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Hirohata S, Hirose S, Miyamoto T. Cerebrospinal fluid IgM, IgA, and IgG indexes in systemic lupus erythematosus. Their use as estimates of central nervous system disease activity. Arch Intern Med. 1985;145:1843–6.CrossRefPubMedGoogle Scholar
  9. 9.
    Iizuka N, et al. Identification of autoantigens specific for systemic lupus erythematosus with central nervous system involvement. Lupus. 2010;19:717–26.CrossRefPubMedGoogle Scholar
  10. 10.
    Arinuma Y, et al. Brain MRI in patients with diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus. Lupus Sci Med. 2014;1:e000050.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Nishimura K, et al. Risperidone in the treatment of acute confusional state (delirium) due to neuropsychiatric lupus erythematosus: case report. Int J Psychiatry Med. 2003;33:299–303.CrossRefPubMedGoogle Scholar
  12. 12.
    Fernandes Moca Trevisani V, Castro AA, Ferreira Neves Neto J, Atallah AN. Cyclophosphamide versus methylprednisolone for treating neuropsychiatric involvement in systemic lupus erythematosus. Cochrane Database Syst Rev. 2013; CD002265.Google Scholar
  13. 13.
    Barile-Fabris L, et al. Controlled clinical trial of IV cyclophosphamide versus IV methylprednisolone in severe neurological manifestations in systemic lupus erythematosus. Ann Rheum Dis. 2005;64:620–5.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Kozora E, Filley CM. Cognitive dysfunction and white matter abnormalities in systemic lupus erythematosus. J Int Neuropsychol Soc. 2011;17:385–92.CrossRefPubMedGoogle Scholar
  15. 15.
    Tomietto P, et al. General and specific factors associated with severity of cognitive impairment in systemic lupus erythematosus. Arthritis Rheum. 2007;57:1461–72.CrossRefPubMedGoogle Scholar
  16. 16.
    Menon S, et al. A longitudinal study of anticardiolipin antibody levels and cognitive functioning in systemic lupus erythematosus. Arthritis Rheum. 1999;42:735–41.CrossRefPubMedGoogle Scholar
  17. 17.
    Hanly JG, et al. A prospective analysis of cognitive function and anticardiolipin antibodies in systemic lupus erythematosus. Arthritis Rheum. 1999;42:728–34.CrossRefPubMedGoogle Scholar
  18. 18.
    McLaurin EY, et al. Predictors of cognitive dysfunction in patients with systemic lupus erythematosus. Neurology. 2005;64:297–303.CrossRefPubMedGoogle Scholar
  19. 19.
    Denburg SD, et al. Corticosteroids and neuropsychological functioning in patients with systemic lupus erythematosus. Arthritis Rheum. 1994;37:1311–20.CrossRefPubMedGoogle Scholar
  20. 20.
    Petri M, et al. Memantine in systemic lupus erythematosus: a randomized, double-blind placebo-controlled trial. Semin Arthritis Rheum. 2011;41:194–202.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Devinsky O, et al. Epilepsy associated with systemic autoimmune disorders. Epilepsy Cur. 2013;13:62–8.CrossRefGoogle Scholar
  22. 22.
    Bluestein HG, et al. Cerebrospinal fluid antibodies to neuronal cells: association with neuropsychiatric manifestations of systemic lupus erythematosus. Am J Med. 1981;70:240–6.CrossRefPubMedGoogle Scholar
  23. 23.
    Arinuma Y, et al. Association of cerebrospinal fluid anti-NR2 glutamate receptor antibodies with diffuse neuropsychiatric systemic lupus erythematosus. Arthritis Rheum. 2008;58:1130–5.CrossRefPubMedGoogle Scholar
  24. 24.
    Yoshio T, et al. Antiribosomal P protein antibodies in cerebrospinal fluid are associated with neuropsychiatric systemic lupus erythematosus. J Rheumatol. 2005;32:34–9.PubMedGoogle Scholar
  25. 25.
    Mitsikostas DD, et al. A meta-analysis for headache in systemic lupus erythematosus: the evidence and the myth. Brain. 2004;127(Pt 5):1200–9.CrossRefPubMedGoogle Scholar
  26. 26.
    Gladman DD, et al. Systemic lupus erythematosus disease activity index 2000. J Rheumatol. 2002;29:288–91.PubMedGoogle Scholar
  27. 27.
    Hanly JG, et al. Headache in systemic lupus erythematosus: results from a prospective, international inception cohort study. Arthritis Rheum. 2013;65:2887–97.CrossRefPubMedGoogle Scholar
  28. 28.
    Dale RC, et al. Antibody binding to neuronal surface in movement disorders associated with lupus and antiphospholipid antibodies. Dev Med Child Neurol. 2011;53:522–8.CrossRefPubMedGoogle Scholar
  29. 29.
    Krakauer M, Law I. FDG PET brain imaging in neuropsychiatric systemic lupus erythematosis with choreic symptoms. Clin Nucl Med. 2009;34:122–3.CrossRefPubMedGoogle Scholar
  30. 30.
    Bala MM, et al. Antiplatelet and anticoagulant agents for secondary prevention of stroke and other thromboembolic events in people with antiphospholipid syndrome. Cochrane Database Syst Rev. 2017;10:CD012169.PubMedGoogle Scholar
  31. 31.
    Fonseca AG, D'Cruz DP. Controversies in the antiphospholipid syndrome: can we ever stop warfarin? J Autoimmune Dis. 2008;5:6.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Carey RA, et al. The effect of adrenocorticotropic hormone (ACTH) and cortisone on the course of disseminated lupus erythematosus and peri-arteritis nodosa. Bull Johns Hopkins Hosp. 1950;87:425–60.PubMedGoogle Scholar
  33. 33.
    Pickering G, et al. Treatment of systemic lupus erythematosus with steroids: report to the Medical Research Council by the collagen diseases and hypersensitivity panel. Br Med J. 1961;2:915–20.CrossRefGoogle Scholar
  34. 34.
    Albert DA, et al. Does corticosteroid therapy affect the survival of patients with systemic lupus erythematosus? Arthritis Rheum. 1979;22:945–53.CrossRefPubMedGoogle Scholar
  35. 35.
    Buttgereit F, et al. Standardised nomenclature for glucocorticoid dosages and glucocorticoid treatment regimens: current questions and tentative answers in rheumatology. Ann Rheum Dis. 2002;61:718–22.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Zhen J, et al. Death-related factors of systemic lupus erythematosus patients associated with the course of disease in Chinese populations: multicenter and retrospective study of 1,958 inpatients. Rheumatol Int. 2013;33(6):1541.CrossRefPubMedGoogle Scholar
  37. 37.
    Jonsen A, et al. Outcome of neuropsychiatric systemic lupus erythematosus within a defined Swedish population: increased morbidity but low mortality. Rheumatology. 2002;41:1308–12.CrossRefPubMedGoogle Scholar
  38. 38.
    Rubin LA, et al. Mortality in systemic lupus erythematosus: the bimodal pattern revisited. Q J Med. 1985;55:87–98.PubMedGoogle Scholar
  39. 39.
    Kasturi S, Sammaritano LR. Corticosteroids in Lupus. Rheum Dis Clin N Am. 2016;42:47–62,viiiCrossRefGoogle Scholar
  40. 40.
    Brown ES, et al. Mood changes during prednisone bursts in outpatients with asthma. J Clin Psychopharmacol. 2002;22:55–61.CrossRefPubMedGoogle Scholar
  41. 41.
    Shimizu Y, et al. Post-steroid neuropsychiatric manifestations are significantly more frequent in SLE compared with other systemic autoimmune diseases and predict better prognosis compared with de novo neuropsychiatric SLE. Autoimmun Rev. 2016;15:786–94.CrossRefPubMedGoogle Scholar
  42. 42.
    Hirohata S, et al. A patient with systemic lupus erythematosus presenting both central nervous system lupus and steroid induced psychosis. J Rheumatol. 1988;15:706–10.PubMedGoogle Scholar
  43. 43.
    Hebert LA, Rovin BH. Oral cyclophosphamide is on the verge of extinction as therapy for severe autoimmune diseases (especially lupus): should nephrologists care? Nephron Clin Pract. 2011;117:c8–14.CrossRefPubMedGoogle Scholar
  44. 44.
    Kivity S, et al. Neuropsychiatric lupus: a mosaic of clinical presentations. BMC Med. 2015;13:43.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Boumpas DT, et al. Pulse cyclophosphamide for severe neuropsychiatric lupus. Q J Med. 1991;81:975–84.CrossRefPubMedGoogle Scholar
  46. 46.
    Neuwelt CM, et al. Role of intravenous cyclophosphamide in the treatment of severe neuropsychiatric systemic lupus erythematosus. Am J Med. 1995;98:32–41.CrossRefPubMedGoogle Scholar
  47. 47.
    Barile L, Lavalle C. Transverse myelitis in systemic lupus erythematosus–the effect of IV pulse methylprednisolone and cyclophosphamide. J Rheumatol. 1992;19:370–2.PubMedGoogle Scholar
  48. 48.
    Baca V, et al. Favorable response to intravenous methylprednisolone and cyclophosphamide in children with severe neuropsychiatric lupus. J Rheumatol. 1999;26:432–9.PubMedGoogle Scholar
  49. 49.
    Martin-Suarez I, et al. Immunosuppressive treatment in severe connective tissue diseases: effects of low dose intravenous cyclophosphamide. Ann Rheum Dis. 1997;56:481–7.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Ramos PC, et al. Pulse cyclophosphamide in the treatment of neuropsychiatric systemic lupus erythematosus. Clin Exp Rheumatol. 1996;14:295–9.PubMedGoogle Scholar
  51. 51.
    Stojanovich L, et al. Neuropsychiatric lupus favourable response to low dose i.v. cyclophosphamide and prednisolone (pilot study). Lupus. 2003;12:3–7.CrossRefPubMedGoogle Scholar
  52. 52.
    Hirano T, et al. Successful therapy with steroid and cyclophosphamide pulse for CNS lupus and lupus myelitis. Jap J Clin Immunol. 2007;30:414–8.CrossRefGoogle Scholar
  53. 53.
    Fanouriakis A, et al. Cyclophosphamide in combination with glucocorticoids for severe neuropsychiatric systemic lupus erythematosus: a retrospective, observational two-centre study. Lupus. 2016;25:627–36.CrossRefPubMedGoogle Scholar
  54. 54.
    Gonzalez LA, et al. Time to neuropsychiatric damage occurrence in LUMINA (LXVI): a multi-ethnic lupus cohort. Lupus. 2009;18:822–30.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Levy Y, et al. A study of 20 SLE patients with intravenous immunoglobulin--clinical and serologic response. Lupus. 1999;8:705–12.CrossRefPubMedGoogle Scholar
  56. 56.
    Sakthiswary R, D'Cruz D. Intravenous immunoglobulin in the therapeutic armamentarium of systemic lupus erythematosus: a systematic review and meta-analysis. Medicine. 2014;93:e86.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Toubi E, et al. High-dose intravenous immunoglobulins: an option in the treatment of systemic lupus erythematosus. Hum Immunoly. 2005;66:395–402.CrossRefGoogle Scholar
  58. 58.
    Milstone AM, et al. Treatment of acute neuropsychiatric lupus with intravenous immunoglobulin (IVIG): a case report and review of the literature. Clin Rheumatol. 2005;24:394–7.CrossRefPubMedGoogle Scholar
  59. 59.
    Engel G, van Vollenhoven RF. Treatment of severe CNS lupus with intravenous immunoglobulin. J Clin Rheumatol. 1999; 5:228–32. Sherer Y, et al. Successful treatment of systemic lupus erythematosus cerebritis with intravenous immunoglobulin. Clin Rheumatol. 1999; 18:170–3.Google Scholar
  60. 60.
    Neuwelt CM. The role of plasmapheresis in the treatment of severe central nervous system neuropsychiatric systemic lupus erythematosus. Ther Apher Dial. 2003;7:173–82.CrossRefPubMedGoogle Scholar
  61. 61.
    Bartolucci P, et al. Adjunctive plasma exchanges to treat neuropsychiatric lupus: a retrospective study on 10 patients. Lupus. 2007;16:817–22.CrossRefPubMedGoogle Scholar
  62. 62.
    Appel GB, et al. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol. 2009;20:1103–12.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Dooley MA, et al. Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis. N Engl J Med. 2011;365:1886–95.CrossRefPubMedGoogle Scholar
  64. 64.
    Tselios K, et al. Mycophenolate Mofetil in nonrenal manifestations of systemic lupus erythematosus: an observational cohort study. J Rheumatol. 2016;43:552–8.CrossRefPubMedGoogle Scholar
  65. 65.
    Ginzler EM, et al. Nonrenal disease activity following mycophenolate mofetil or intravenous cyclophosphamide as induction treatment for lupus nephritis: findings in a multicenter, prospective, randomized, open-label, parallel-group clinical trial. Arthritis Rheum. 2010;62:211–21.CrossRefPubMedGoogle Scholar
  66. 66.
    Conti F, et al. Mycophenolate mofetil in systemic lupus erythematosus: results from a retrospective study in a large monocentric cohort and review of the literature. Immunol Res. 2014;60:270–6.CrossRefPubMedGoogle Scholar
  67. 67.
    Lhotta K, et al. Cerebral vasculitis in a patient with hereditary complete C4 deficiency and systemic lupus erythematosus. Lupus. 2004;13:139–41.CrossRefPubMedGoogle Scholar
  68. 68.
    Jose J, et al. Mycophenolate mofetil in neuropsychiatric systemic lupus erythematosus. Indian J Med Sci. 2005;59:353–6.CrossRefPubMedGoogle Scholar
  69. 69.
    Higashioka K, et al. Successful treatment of lupus cerebrovascular disease with mycophenolate mofetil. Intern Med. 2015;54:2255–9.CrossRefPubMedGoogle Scholar
  70. 70.
    Mok CC, et al. Mycophenolate mofetil for lupus related myelopathy. Ann Rheum Dis. 2006;65:971–3.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Saison J, et al. Systemic lupus erythematosus-associated acute transverse myelitis: manifestations, treatments, outcomes, and prognostic factors in 20 patients. Lupus. 2015;24:74–81.CrossRefPubMedGoogle Scholar
  72. 72.
    Gordon C, Amissah-Arthur MB, Gayed M, Brown S, Bruce IN, D'Cruz D, et al. The British Society for Rheumatology guideline for the management of systemic lupus erythematosus in adults. Rheumatology. 2018;57:e1–e45.CrossRefPubMedGoogle Scholar
  73. 73.
    Feng L, et al. Mycophenolate mofetil versus azathioprine as maintenance therapy for lupus nephritis: a meta-analysis. Nephrology. 2013;18:104–10.CrossRefPubMedGoogle Scholar
  74. 74.
    Mok CC, et al. Treatment of lupus psychosis with oral cyclophosphamide followed by azathioprine maintenance: an open-label study. Am J Med. 2003;115:59–62.CrossRefPubMedGoogle Scholar
  75. 75.
    Ginzler E, et al. Long-term maintenance therapy with azathioprine in systemic lupus erythematosus. Arthritis Rheum. 1975;18:27–34.CrossRefPubMedGoogle Scholar
  76. 76.
    Tokunaga M, et al. Efficacy of rituximab (anti-CD20) for refractory systemic lupus erythematosus involving the central nervous system. Ann Rheum Dis. 2007;66:470–5.CrossRefPubMedGoogle Scholar
  77. 77.
    Narvaez J, Rios-Rodriguez V, de la Fuente D, Estrada P, Lopez-Vives L, Gomez-Vaquero C, et al. Rituximab therapy in refractory neuropsychiatric lupus: current clinical evidence. Semin Arthritis Rheum. 2011;41:364–72.CrossRefPubMedGoogle Scholar
  78. 78.
    Dale RC, et al. Utility and safety of rituximab in pediatric autoimmune and inflammatory CNS disease. Neurology. 2014;83:142–50.CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Furie R, et al. A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum. 2011;63:3918–30.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Navarra SV, et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377:721–31.CrossRefPubMedGoogle Scholar
  81. 81.
    Manzi S, et al. Effects of belimumab, a B lymphocyte stimulator-specific inhibitor, on disease activity across multiple organ domains in patients with systemic lupus erythematosus: combined results from two phase III trials. Ann Rheum Dis. 2012;71:1833–8.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Hirohata S. 110th scientific meeting of the Japanese society of internal medicine: invited lecture: 5. Neurological involvement in connective tissue diseases. Nippon Naika Gakkai Zasshi. 2013;102:2214–23.CrossRefPubMedGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of RheumatologyTokyo Medical University HospitalTokyoJapan

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