J Korean Rheum Assoc.  2008 Jun;15(2):170-174. 10.4078/jkra.2008.15.2.170.

Successful Treatment of Neuropsychiatric Syndrome with Rituximab in a Patient with Systemic Lupus Erythematosus and Dermatomyositis Overlap Syndrome

• Lee SG
• Yoo B
• Kim KM
• Choi HO
• Oh JS
• Nah SS
• Kim YG
• Lee CK

• KMID: 1270235
• DOI: http://doi.org/10.4078/jkra.2008.15.2.170

Abstract

A 31-year-old woman was referred to our hospital and diagnosed as overlap syndrome with systemic lupus erythematosus and dermatomyositis. After completing the fourth cycle of intravenous immunoglobulin therapy, the patient developed acute confusional state with the Glasgow Coma Scale of 7. Considering the lack of response to high dose corticosteroid therapy (methylprednisolone 1 g per day for 3 days), rituximab (500 mg per week) was administered twice. The next day after the administration of the first dose of rituximab, the level of consciousness started to improve and 15 days after rituximab, mental status was fully recovered. The proportion of CD19+ B cells started to decrease within 1 week after the administration of rituximab and remained depleted for 14 weeks. There was also a gradual decrease in serum CD40 and CD80 concentration measured by ELISA up to 4 months. This case suggests the effect of rituximab for the treatment of neuropsychiatric lupus.

Keyword

Central nervous system lupus; Rituximab; CD40; CD80

MeSH Terms

Female
Humans

Figure

• 

  Fig. 1. Serial changes in the proportion of CD19 (＋) lymphocytes, the concentration of C3 and C4, and the dosage of prednisolone. Transverse axis indicates days after the administration of rituximab. C: complement.

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  Fig. 2. Serial change in the concentration of CD40 and CD80. Transverse axis indicates days after the administration of Rituximab. Vertical axis indicates the concentration of CD40 and CD80 measured by ELISA. (Reference value, CD40:7.8 ∼500 pg/mL, CD80:320∼20.000 pg/mL)

Reference

References

1. Hanly JG, Urowitz MB, Sanchez-Guerrero J, Bae SC, Gordon C, Wallace DJ, et al. Neuropsychiatric events at the time of diagnosis of systemic lupus erythematosus: an international inception cohort study. Arthritis Rheum. 2007; 56:265–73.

2. Blanco FJ, Gomez-Reino JJ, de la Mata J, Corrales A, Rodriguez-Valverde V, Rosas JC, et al. Survival analysis of 306 European Spanish patients with systemic lupus erythematosus. Lupus. 1998; 7:159–63.

3. Reff ME, Carner K, Chambers KS, Chinn PC, Leonard JE, Raab R, et al. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood. 1994; 83:435–45.

4. Tokunaga M, Saito K, Kawabata D, Imura Y, Fujii T, Nakayamada S, et al. Efficacy of rituximab (anti-CD20) for refractory systemic lupus erythematosus involving the central nervous system. Ann Rheum Dis. 2007; 66:470–5.

5. Tokunaga M, Fujii K, Saito K, Nakayamada S, Tsujimura S, Nawata M, et al. Downregulation of CD40 and CD80 on B cells in patients with life-threatening systemic lupus erythematosus after successful treatment with rituximab. Rheumatology (Oxford). 2005; 44:176–82.

6. Leandro MJ, Cambridge G, Edwards JC, Ehrenstein MR, Isenberg DA. B-cell depletion in the treatment of patients with systemic lupus erythematosus: a longitudinal analysis of 24 patients. Rheumatology (Oxford). 2005; 44:1542–5.

7. Looney RJ, Anolik JH, Campbell D, Felgar RE, Young F, Arend LJ, et al. B cell depletion as a novel treatment for systemic lupus erythematosus: a phase I/II dose-escalation trial of rituximab. Arthritis Rheum. 2004; 50:2580–9.

8. Leandro MJ, Edwards JC, Cambridge G, Ehrenstein MR, Isenberg DA. An open study of B lymphocyte depletion in systemic lupus erythematosus. Arthritis Rheum. 2002; 46:2673–7.

9. Abbott NJ, Mendonca LL, Dolman DE. The blood-brain barrier in systemic lupus erythematosus. Lupus. 2003; 12:908–15.

10. Contin C, Pitard V, Itai T, Nagata S, Moreau JF, Dechanet-Merville J. Membrane-anchored CD40 is processed by the tumor necrosis factor-alpha-converting enzyme. Implications for CD40 signaling. J Biol Chem. 2003; 278:32801–9.

11. van Kooten C, Gaillard C, Galizzi JP, Hermann P, Fossiez F, Banchereau J, et al. B cells regulate expression of CD40 ligand on activated T cells by lowering the mRNA level and through the release of soluble CD40. Eur J Immunol. 1994; 24:787–92.

12. Desai-Mehta A, Lu L, Ramsey-Goldman R, Datta SK. Hyperexpression of CD40 ligand by B and T cells in human lupus and its role in pathogenic autoantibody production. J Clin Invest. 1996; 97:2063–73.

13. Grammer A, Shinohara S, Vazquez E, Gur H, Illei G, Lipsky P. Normalization of peripheral B cells following treatment of active SLE patients with humanized anti-CD154 (5c8, BG9588). Arthritis Rheum. 2001; 44:S282.

14. Wong CK, Lit LC, Tam LS, Li EK, Lam CW. Aberrant production of soluble costimulatory molecules CTLA-4, CD28, CD80 and CD86 in patients with systemic lupus erythematosus. Rheumatology (Oxford). 2005; 44:989–94.