Abstract
Psychiatric manifestations are relatively common in systemic lupus erythematosus (SLE) patients. Since there are factors causing psychiatric manifestations other than SLE, the diagnosis of lupus psychosis (LP) is often difficult. Previous studies disclosed that cerebrospinal fluid (CSF) IL-6 was elevated in SLE patients with neuropsychiatric manifestation. The current studies were therefore designed to examine the efficacy of CSF IL-6 in diagnosis of LP. Multicenter retrospective study was performed with 45 SLE patients who showed psychiatric manifestations between 1993 and 2000. The diagnosis of LP and psychosis due to causes other than SLE (non-LP) was confirmed by retrospective review of the clinical records. Thirty-two of the 45 patients were reconfirmed as LP in the retrospective study. Receiver operating characteristic curve analysis revealed that the sensitivity and specificity of CSF IL-6 for diagnosis of LP were 87.5% and 92.3%, respectively, at the cut-off value of 4.3 pg/ml. These results indicate that CSF IL-6 might be an effective measure in diagnosing LP, although exclusion of infectious meningoencephalitis and cerebrovascular accident is necessary.
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References
Gibson T, Myers AR (1975) Nervous system involvement in systemic lupus erythematosus. Ann Rheum Dis 35:398–406
Harris EN, Hughes GR (1985) Cerebral disease in systemic lupus erythematosus. Springer Semin Immunopathol 8:251–266
ACR Ad Hoc Committee on Neuropsychiatric Lupus Nomenclature (1999) The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum 42:599–608
Hermosillo-Romo D, Brey RL (2002) Diagnosis and management of patients with neuropsychiatric systemic lupus erythematosus (NPSLE). Best Pract Res Clin Rheumatol 16:229–244
West SG (1994) Neuropsychiatric lupus. Rheum Dis Clin North Am 20:129–158
Hirohata S, Miyamoto T (1990) Elevated levels of interleukin-6 in cerebrospinal fluid from patients with systemic lupus erythematosus and central nervous system involvement. Arthritis Rheum 33:644–649
Trysberg E, Carlsten H, Tarkowski A (2000) Intrathecal cytokines in systemic lupus erythematosus with central nervous system involvement. Lupus 9:498–503
Fragoso-Loyo H, Richaud-Patin Y, Orozco-Narváez A, Dávila-Maldonado L, Atisha-Fregoso Y, Llorente L, Sánchez-Guerrero J (2007) Interleukin-6 and chemokines in the neuropsychiatric manifestations of systemic lupus erythematosus. Arthritis Rheum 56:1242–1250
Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF et al (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277
Link H, Tibbling G (1977) Principles of albumin and IgG analyses in neurological disorders. III. Evaluation of IgG synthesis within the central nervous system in multiple sclerosis. Scand J Clin Lab Invest 37:397–401
Vila N, Castillo J, Davalos A, Chamorro A (2000) Proinflammatory cytokines and early neurological worsening in ischemic stroke. Stroke 31:2325–2329
Torre D, Zeroli C, Ferraro G, Speranza F, Tambini R, Martegani R, Fiori GP (1992) Cerebrospinal fluid levels of IL-6 in patients with acute infections of the central nervous system. Scand J Infect Dis 24:787–791
Trysberg E, Blennow K, Zachrisson O, Tarkowski A (2004) Intrathecal levels of matrix metalloproteinases in systemic lupus erythematosus with central nervous system engagement. Arthritis Res Ther 6:R551–R556
Kimura M, Aramaki K, Wada T, Nishi K, Matsushita R, Iizuka N, Hashimoto A, Tanaka S, Ishikawa A, Endo H, Hirohata S (2008) Reversible focal neurological deficits in systemic lupus erythematosus: report of 2 cases and review of the literature. J Neurol Sci 272:71–76
Winfield JB, Shaw M, Silverman LM, Eisenberg RA, Wilson HA 3rd, Koffler D (1983) Intrathecal IgG synthesis and blood–brain barrier impairment in patients with systemic lupus erythematosus and central nervous system dysfunction. Am J Med 74:837–844
Hirohata S, Hirose S, Miyamoto T (1985) Cerebrospinal fluid IgM, IgA, and IgG indexes in systemic lupus erythematosus. Their use as estimates of central nervous system disease activity. Arch Intern Med 145:1843–1846
Hirohata S, Inoue T, Yamada A, Hirose S, Miyamoto T (1984) Quantitation of IgG, IgA and IgM in the cerebrospinal fluid by a solid-phase enzyme-immunoassay. Establishment of normal control values. J Neurol Sci 63:101–110
Hirohata S, Yamada A, Inoue T (1985) A sensitive and simple method for determination of IgM in cerebrospinal fluid by a solid-phase enzyme-immunoassay. Comparison of two different methods. J Neurol Sci 67:115–118
Bonfa E, Golombek SJ, Kaufman LD, Skelly S, Weissbach H, Brot N et al (1987) Association between lupus psychosis and anti-ribosomal P protein antibodies. N Engl J Med 317:265–271
Isshi K, Hirohata S (1996) Association of anti-ribosomal P protein antibodies with neuropsychiatric systemic lupus erythematosus. Arthritis Rheum 39:1483–1490
Karassa FB, Afeltra A, Ambrozic A, Chang DM, De Keyser F, Doria A et al (2006) Accuracy of anti-ribosomal P protein antibody testing for the diagnosis of neuropsychiatric systemic lupus erythematosus: an international meta-analysis. Arthritis Rheum 54:312–324
Bluestein HG, Williams GW, Steinberg AD (1981) Cerebrospinal fluid antibodies to neuronal cells: association with neuropsychiatric manifestations of systemic lupus erythematosus. Am J Med 70:240–246
Isshi K, Hirohata S (1998) Differential roles of the anti-ribosomal P antibody and antineuronal antibody in the pathogenesis of central nervous system involvement in systemic lupus erythematosus. Arthritis Rheum 41:1819–1827
Hirohata S, Arinuma Y, Takayama M, Yoshio T (2007) Association of cerebrospinal fluid anti-ribosomal p protein antibodies with diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus. Arthritis Res Ther 9:R44
Arinuma Y, Yanagida T, Hirohata S (2008) Association of cerebrospinal fluid anti-NR2 glutamate receptor antibodies with diffuse neuropsychiatric systemic lupus erythematosus. Arthritis Rheum 58:1130–1135
Acknowledgments
The authors wish to thank Dr. Masako Hara from Tokyo Women’s Medical University, Dr. Tetsuo Kubota from Graduate School of Health Science, Tokyo Medical and Dental University (members of NPSLE Research Subcommittee), and other members of the Research Committee for their help in obtaining data and helpful discussion. This work was supported by 2002–2004 research grants from the Ministry of Health, Labor and Welfare of the Japanese Government.
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Hirohata, S., Kanai, Y., Mitsuo, A. et al. Accuracy of cerebrospinal fluid IL-6 testing for diagnosis of lupus psychosis. A multicenter retrospective study. Clin Rheumatol 28, 1319–1323 (2009). https://doi.org/10.1007/s10067-009-1226-8
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DOI: https://doi.org/10.1007/s10067-009-1226-8