Failure of treatment of myasthenia gravis by cyclosporin-A: a case report

Marchiori, Paulo E.; Assis, J. Lamartine de; Scaff, Milberto

doi:10.1590/S0004-282X1989000100013

Abstracts

Recently, cyclosporin-A (Cy-A) has been used in the treatment oy myasthenia gravis (MG). This drug could be employed in some patients refractory to classic treatments or that develop undesirable side effects. It is reported the case of a 22 year-old woman with generalized and severe MG, and diabetes mellitus. She had been submitted to thymectomy and reoperated, to the classic ethiopathogenic methods of therapy, and to total body irradiation. No therapeutical results were observed. Also, she developed transient and slow bone marrow depression, and liver dysfunction. Owing to these limitations and to the absence of response to treatments mentioned, Cy-A use was attempted in this case. Unfortunately, Cy-A did not influence the myasthenic symptomatology. Cy-A also failed in suppressing anti-AChR production, which increased during Cy-A therapy. Results observed in this case are in disagreement with literature data on the subject.

A ciclosporina-A (Ci-A) foi incluída, recentemente, no esquema de tratamento da miastenia grave (MG). A droga tornou-se opqão válida para pacientes refratários a outros métodos terapêuticos de base etiopatogênica ou em virtude de efeitos colaterais e con-tra-indicações importantes a tais procedimentos. É registrado o caso de mulher de 22 anos de idade com forma generalizada e severa de MG adquirida e com diabetes mellitus. Foi timectomizada e reoperada ulteriormente. O diabetes se agravou com glicocorticóides e a paciente desenvolveu depressão da medula óssea e, por último, comprometimento hepático após uso de citostáticos. Não tendo havido resposta à irradiação de corpo inteiro, optou-se, então, pelo uso da Ci-A que também não influenciou a sintomatologia miastênica. É de notar que dosagens repetidas de anti-receptor de acetilcolina durante o uso de Ci-A, mostrou produção aumentada do anticorpo, em desacordo com os dados da literatura.

Failure of treatment of myasthenia gravis by cyclosporin-A: a case report

Ausência de resposta ao tratamento da miastenia grave por ciclosporina-A: registro de um caso

Paulo E. Marchiori^I; J. Lamartine de Assis^II; Milberto Scaff^II

^IDepartment of Neurology, Faculty of Medicine, University of São Paulo (FMUSP): Assistant Professor

^IIDepartment of Neurology, Faculty of Medicine, University of São Paulo (FMUSP): Associate Professor

SUMMARY

Recently, cyclosporin-A (Cy-A) has been used in the treatment oy myasthenia gravis (MG). This drug could be employed in some patients refractory to classic treatments or that develop undesirable side effects. It is reported the case of a 22 year-old woman with generalized and severe MG, and diabetes mellitus. She had been submitted to thymectomy and reoperated, to the classic ethiopathogenic methods of therapy, and to total body irradiation. No therapeutical results were observed. Also, she developed transient and slow bone marrow depression, and liver dysfunction. Owing to these limitations and to the absence of response to treatments mentioned, Cy-A use was attempted in this case. Unfortunately, Cy-A did not influence the myasthenic symptomatology. Cy-A also failed in suppressing anti-AChR production, which increased during Cy-A therapy. Results observed in this case are in disagreement with literature data on the subject.

RESUMO

A ciclosporina-A (Ci-A) foi incluída, recentemente, no esquema de tratamento da miastenia grave (MG). A droga tornou-se opqão válida para pacientes refratários a outros métodos terapêuticos de base etiopatogênica ou em virtude de efeitos colaterais e con-tra-indicações importantes a tais procedimentos. É registrado o caso de mulher de 22 anos de idade com forma generalizada e severa de MG adquirida e com diabetes mellitus. Foi timectomizada e reoperada ulteriormente. O diabetes se agravou com glicocorticóides e a paciente desenvolveu depressão da medula óssea e, por último, comprometimento hepático após uso de citostáticos. Não tendo havido resposta à irradiação de corpo inteiro, optou-se, então, pelo uso da Ci-A que também não influenciou a sintomatologia miastênica. É de notar que dosagens repetidas de anti-receptor de acetilcolina durante o uso de Ci-A, mostrou produção aumentada do anticorpo, em desacordo com os dados da literatura.

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Clínica Neurológica, FMUSP - Caixa Postal 3461 - 01051 São Paulo SP - Brasil

1. Appel SH, Blosser, JC, McManaman JL, Ashizawa T - Acetylcholine receptor turnover in myasthenia gravis. Am J Physiol 243:E31, 1982.
2. Besinger VA, Mraz W, Fateh-Moghadam A - Cyclosporin (CyA) in myasthenia gravis. In Schindler R (ed): Cyclosporin in Autoimmune Diseases, First International Symposium, Bade Springer, Berlin, 1985, pg 100.
3. Dos Reis GA, Shevach EM - Effect of cyclosporin-A on T cell function in vitro: the mechanism of suppression of T cell proliferation depends on the nature of the T cell stimulus as well as the differentiation state of the responding T cell. J Immunol 129 :2360, 1982.
4. Drachman DB, Adams RN, Mcintosh K, Pestronk A - Treatment of experimental myasthenia gravis with cyclosporin A. Clin Immunol Immunopathol 34:174, 1985.
5. Engel AG, Sahashi K, Fumagalli G - The immunopathology of acquired myasthenia gravis. Ann NY Acad Sci 377:158, 1981.
6. Fambrough BM, Drachman DB, Satyamurti S - Neuromuscular junction in myasthenia gravis: decreased acetylcholine receptors. Science 182:293, 1973.
7. Hess AD, Tutschka PJ - Effect of cyclosporin A on human lymphocyte responses in vitro: I. C_s A allows for the expression of alloantigen-activated suppression cells while preferentially inhibiting the induction of cytolytic effector lymphocytes in MLR. J Immunol 124:2601, 1980.
8. Hess AD, Tutschka PJ, Santos GW - Effect of cyclosporin-A on human lymphocyte responses in vitro: II. Induction of specific alloantigen unresponsiveness mediated by a nylon wool adherent suppressor cell. J Immumol 126:961, 1981.
9. Lennon VA, Lindstrom JM, Seybold ME - Experimental autoimmune myasthenia: a model of myasthenia gravis in rats and guinea pigs. J Exp Med 141:1365, 1975.
10. Lindstrom JM, Seybold ME, Lennon VA, Whittinghams S, Duane DD - Antibody to acetylcholine receptor in myasthenia gravis: clinical correlates and diagnostic values. Neurology 26:1054, 1976.
11. Nyberg-Hansen R, Gjerstad L - Cyclosporin in the treatment of myasthenia gravis: preliminary results from pilot study. In Schindler R (ed) : Cyclosporin in Autoimmune Diseases, First International Symposium, Bade Springer, Berlin, 1985, pg 96.
12. Wang BS, Heacock EH, Chang-Xue Z, Tilney NL, Strom TB, Mannick JA - Evidence for the presence of suppressor T lymphocytes in animals treated with cyclosporin-A. J Immunol 128:1382, 1982.

Publication Dates

Publication in this collection
06 June 2011
Date of issue
Mar 1989

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Appel SH, Blosser, JC, McManaman JL, Ashizawa T - Acetylcholine receptor turnover in myasthenia gravis. Am J Physiol 243:E31, 1982.

[2] 2. Besinger VA, Mraz W, Fateh-Moghadam A - Cyclosporin (CyA) in myasthenia gravis. In Schindler R (ed): Cyclosporin in Autoimmune Diseases, First International Symposium, Bade Springer, Berlin, 1985, pg 100.

[3] 3. Dos Reis GA, Shevach EM - Effect of cyclosporin-A on T cell function in vitro: the mechanism of suppression of T cell proliferation depends on the nature of the T cell stimulus as well as the differentiation state of the responding T cell. J Immunol 129 :2360, 1982.

[4] 4. Drachman DB, Adams RN, Mcintosh K, Pestronk A - Treatment of experimental myasthenia gravis with cyclosporin A. Clin Immunol Immunopathol 34:174, 1985.

[5] 5. Engel AG, Sahashi K, Fumagalli G - The immunopathology of acquired myasthenia gravis. Ann NY Acad Sci 377:158, 1981.

[6] 6. Fambrough BM, Drachman DB, Satyamurti S - Neuromuscular junction in myasthenia gravis: decreased acetylcholine receptors. Science 182:293, 1973.

[7] 7. Hess AD, Tutschka PJ - Effect of cyclosporin A on human lymphocyte responses in vitro: I. C_s A allows for the expression of alloantigen-activated suppression cells while preferentially inhibiting the induction of cytolytic effector lymphocytes in MLR. J Immunol 124:2601, 1980.

[8] 8. Hess AD, Tutschka PJ, Santos GW - Effect of cyclosporin-A on human lymphocyte responses in vitro: II. Induction of specific alloantigen unresponsiveness mediated by a nylon wool adherent suppressor cell. J Immumol 126:961, 1981.

[9] 9. Lennon VA, Lindstrom JM, Seybold ME - Experimental autoimmune myasthenia: a model of myasthenia gravis in rats and guinea pigs. J Exp Med 141:1365, 1975.

[10] 10. Lindstrom JM, Seybold ME, Lennon VA, Whittinghams S, Duane DD - Antibody to acetylcholine receptor in myasthenia gravis: clinical correlates and diagnostic values. Neurology 26:1054, 1976.

[11] 11. Nyberg-Hansen R, Gjerstad L - Cyclosporin in the treatment of myasthenia gravis: preliminary results from pilot study. In Schindler R (ed) : Cyclosporin in Autoimmune Diseases, First International Symposium, Bade Springer, Berlin, 1985, pg 96.

[12] 12. Wang BS, Heacock EH, Chang-Xue Z, Tilney NL, Strom TB, Mannick JA - Evidence for the presence of suppressor T lymphocytes in animals treated with cyclosporin-A. J Immunol 128:1382, 1982.