Miastenia grave induzida por D-penicilamina em paciente com esclerose sistêmica progressiva

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

doi:10.1590/S0004-282X1984000400010

Resumos

Relato de caso de miastenia grave induzida por D-penicilamina. São descutidos os possíveis mecanismos etiopatogênicos envolvidos no desencadeamento da doença e é salientada a presença de anticorpo anti-receptor de acetilcolina e hiperplasia tímica na DPA-MG.

The development of autoimmune diseases in some patients treated with D-penicillamine (DPA) suggests that the reported occurrence of a conduction disorder at the neuromuscular junction and the development of a reversible myasthenia gravis in rheumatoid disease, progressive systemic sclerosis or Wilson's disease after the use of DPA are part of a general predisposition for autoimmune disease related to DPA therapy. The case reported is an example. The DPA- induced myasthenia gravis (MO) is similar to the spontaneous MG clinically and electrophysiologically, though ocular signs prevail in the former. Antibodies to acetylcholine receptor have been demonstrated and thymic hyperplasia also has been formed. Regarding the onset of myasthenic manifestations the duration of the treatment with DPA varies from 6 to 10 months. The action of DPA on the neuromuscular junction is different from that occurring in spontaneous MG. The pathogenesis of the DPA induced MG is still obscure. The chemical properties of DPA permit it to react with many proteins and some alteration of proteins may appear, with structural changes in the composition and antigenicity of the collagen fibers. In vitro DPA causes disorder of acetylcholine receptor bridges to a,b,g sub-units with reduction of the S-S bridges in the g-subunit. This decreases the linkage of high affinity and abolishes its positive cooperative system, reducing the S-S connection in the a-unit near the acetylcholine linkage. The interation between DPA and receptor may induce antigenic alteration in this latter, starting the autoimmune phenomena. The other possibility is the stimulation of prostaglandin E-l synthesis by DPA may fill the allosteric place of ACh receptor, interfering on the neuromuscular junction.

Miastenia grave induzida por D-penicilamina em paciente com esclerose sistêmica progressiva

Myasthenia gravis induced by D-penicillamine in a progressive systemic sclerosis case

Paulo E. Marchiori^I; Milberto Scaff^II; Wilson Cossermelli^III; J. Lamartine de Assis^IV

^IMédico Assistente. Disciplina de Neurologia Clínica, Departamentos de Neuropsiquiatria e de Clínica Médica da Faculdade de Medicina da Universidade de São Paulo (FMUSP)

^IIProfessor Livre Docente. Disciplina de Neurologia Clínica, Departamentos de Neuropsiquiatria e de Clínica Médica da Faculdade de Medicina da Universidade de São Paulo (FMUSP)

^IIIProfessor Titular. Disciplina de Neurologia Clínica, Departamentos de Neuropsiquiatria e de Clínica Médica da Faculdade de Medicina da Universidade de São Paulo (FMUSP)

^IVProfessor Adjunto. Disciplina de Reumatologia, Departamentos de Neuropsiquiatria e de Clínica Médica da Faculdade de Medicina da Universidade de São Paulo (FMUSP)

RESUMO

Relato de caso de miastenia grave induzida por D-penicilamina. São descutidos os possíveis mecanismos etiopatogênicos envolvidos no desencadeamento da doença e é salientada a presença de anticorpo anti-receptor de acetilcolina e hiperplasia tímica na DPA-MG.

SUMMARY

The development of autoimmune diseases in some patients treated with D-penicillamine (DPA) suggests that the reported occurrence of a conduction disorder at the neuromuscular junction and the development of a reversible myasthenia gravis in rheumatoid disease, progressive systemic sclerosis or Wilson's disease after the use of DPA are part of a general predisposition for autoimmune disease related to DPA therapy. The case reported is an example. The DPA- induced myasthenia gravis (MO) is similar to the spontaneous MG clinically and electrophysiologically, though ocular signs prevail in the former. Antibodies to acetylcholine receptor have been demonstrated and thymic hyperplasia also has been formed. Regarding the onset of myasthenic manifestations the duration of the treatment with DPA varies from 6 to 10 months. The action of DPA on the neuromuscular junction is different from that occurring in spontaneous MG. The pathogenesis of the DPA induced MG is still obscure. The chemical properties of DPA permit it to react with many proteins and some alteration of proteins may appear, with structural changes in the composition and antigenicity of the collagen fibers. In vitro DPA causes disorder of acetylcholine receptor bridges to a,b,g sub-units with reduction of the S-S bridges in the g-subunit. This decreases the linkage of high affinity and abolishes its positive cooperative system, reducing the S-S connection in the a-unit near the acetylcholine linkage. The interation between DPA and receptor may induce antigenic alteration in this latter, starting the autoimmune phenomena. The other possibility is the stimulation of prostaglandin E-l synthesis by DPA may fill the allosteric place of ACh receptor, interfering on the neuromuscular junction.

Texto completo disponível apenas em PDF.

Full text available only in PDF format.

Trabalho realizado nas Disciplinas de Neurologia Clínica e de Reumatologia dos Departamentos de Neuropsiquiatria e de Clínica Médica da Faculdade de Medicina da Universidade de São Paulo (FMUSP).

Clínica Neurológica, Hospital das Clínicas, FMUSP - Caixa Postal 3461 - 01000, São Paulo, SP - Brasil.

1. BEHAN, P. - Immune disease and HLA association with myasthenia gravis. J. Neurol. Neurosurg. Psychiat. 43:611, 1980.
2. BEVER, C; WONG CHANG, H.; PENN, S.A.; JAFFE, A.I. & BOCK, E. - Chemical alteration of AChR by penicillamine: a mechanism for the induction of myasthenia gravis. Neurology (NY) 31:84, 1981.
3. BEVER, C.T.; WONG CHANG, H.; PENN, A.S.; JAFFE, A.I. & BOCK, E. - Penicillamine on acetylcholine receptor. Neurology (NY) 32:1077, 1982.
4. BUCKNALL, R.C.; DIXON, A.S.T.J.; GLICK, E.N.; WOOLAND, J. & ZUTSCHI, E.W. - Myasthenia gravis associated with penicillamine treatment for rheumatoid arthritis. Brit. med. J. 1:600, 1975.
5. BURRES, S.A.; KANTER. M.E.; RICHMAN, D.P. & ARNARON, B.G.W. - Studies on the pathophysiology of chronic D-penicillamine-induced myasthenia. Ann. N.Y. Acad. Sci. 377:640, 1981.
6. EPSTEIN, O.; De VILLIERS, D.; JAIN, S.; POTTER, B.J.; THOMAS, H.C. & SHERLOCK, S. - Reduction of immune complexes and immunoglobulins induced by penicillamine in primary biliary cirrhosis. N. Engl. J. Med. 300:274, 1979.
7. HERBERT, C.M.; LINDBERG, K.A.; JAYSON, M.I.V. & BELI, A.J. - Biosynthesis and maturation of skin collagen in scleroderma: the effect of D-penicillamine. Lancet 1:187-192, 1974.
8. HORROBIN, D.F. - Myasthenia and prostaglandin E-1. Ann. int. Med. 90:719, 1979.
9. MUERS, M. & STOKES, W. - Treatment of scleroderma heart by D-penicillamine. Brit. Heart J. 38:864, 1976.
10. MITCHEL, G.W.; LICHTENFELD, P.J. & McDONALD, C.J. - Myasthenia gravis and scleroderma. J. amer. med. Assoc. 233:531, 1975.
11. RUSSEL, A.S. & LINDSTROM, J.M. - Penicillamine-induced myasthenia gravis associated with antibodies to acetylcholine receptor. Neurology (Minneapolis) 28:847, 1978.
12. STALBERG, E. - Clinical electrophysiology in myasthenia gravis. J. Neurol. Neurosurg. Psychiat. 43:622, 1980.
13. SYMPSON, J.A. - Myasthenia gravis: a personal view of pathogenesis and mechanism. Muscle Nerve 1:45, 1978.
14. TORRES, F.C.; GRIGGS, R.C.; BAUM, J. & PENN, S.A. - Penicillamine-induced myasthenia gravis in progressive systemic sclerosis. Arthritis. Rheumat. 23:505, 1980.

Datas de Publicação

Publicação nesta coleção
13 Ago 2012
Data do Fascículo
Dez 1984

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

[1] 1. BEHAN, P. - Immune disease and HLA association with myasthenia gravis. J. Neurol. Neurosurg. Psychiat. 43:611, 1980.

[2] 2. BEVER, C; WONG CHANG, H.; PENN, S.A.; JAFFE, A.I. & BOCK, E. - Chemical alteration of AChR by penicillamine: a mechanism for the induction of myasthenia gravis. Neurology (NY) 31:84, 1981.

[3] 3. BEVER, C.T.; WONG CHANG, H.; PENN, A.S.; JAFFE, A.I. & BOCK, E. - Penicillamine on acetylcholine receptor. Neurology (NY) 32:1077, 1982.

[4] 4. BUCKNALL, R.C.; DIXON, A.S.T.J.; GLICK, E.N.; WOOLAND, J. & ZUTSCHI, E.W. - Myasthenia gravis associated with penicillamine treatment for rheumatoid arthritis. Brit. med. J. 1:600, 1975.

[5] 5. BURRES, S.A.; KANTER. M.E.; RICHMAN, D.P. & ARNARON, B.G.W. - Studies on the pathophysiology of chronic D-penicillamine-induced myasthenia. Ann. N.Y. Acad. Sci. 377:640, 1981.

[6] 6. EPSTEIN, O.; De VILLIERS, D.; JAIN, S.; POTTER, B.J.; THOMAS, H.C. & SHERLOCK, S. - Reduction of immune complexes and immunoglobulins induced by penicillamine in primary biliary cirrhosis. N. Engl. J. Med. 300:274, 1979.

[7] 7. HERBERT, C.M.; LINDBERG, K.A.; JAYSON, M.I.V. & BELI, A.J. - Biosynthesis and maturation of skin collagen in scleroderma: the effect of D-penicillamine. Lancet 1:187-192, 1974.

[8] 8. HORROBIN, D.F. - Myasthenia and prostaglandin E-1. Ann. int. Med. 90:719, 1979.

[9] 9. MUERS, M. & STOKES, W. - Treatment of scleroderma heart by D-penicillamine. Brit. Heart J. 38:864, 1976.

[10] 10. MITCHEL, G.W.; LICHTENFELD, P.J. & McDONALD, C.J. - Myasthenia gravis and scleroderma. J. amer. med. Assoc. 233:531, 1975.

[11] 11. RUSSEL, A.S. & LINDSTROM, J.M. - Penicillamine-induced myasthenia gravis associated with antibodies to acetylcholine receptor. Neurology (Minneapolis) 28:847, 1978.

[12] 12. STALBERG, E. - Clinical electrophysiology in myasthenia gravis. J. Neurol. Neurosurg. Psychiat. 43:622, 1980.

[13] 13. SYMPSON, J.A. - Myasthenia gravis: a personal view of pathogenesis and mechanism. Muscle Nerve 1:45, 1978.

[14] 14. TORRES, F.C.; GRIGGS, R.C.; BAUM, J. & PENN, S.A. - Penicillamine-induced myasthenia gravis in progressive systemic sclerosis. Arthritis. Rheumat. 23:505, 1980.