D-Penicillamine-lnduced Myasthenia Gravis in Rheumatoid Arthritis D - P E N I C I L L A M I N E is used for the treatment of active rheumatoid arthritis, Wilson's Disease, and cystinuria. It has been reported to be implicated as a cause of a u t o i m m u n e diseases and serologic autoantibodies. Clinical pictures indistinguishable from lupus e r y t h e m a t o s u s (1), Goodpasture's s y n d r o m e (2), and p o l y m y o s i t i s (3) have been reported as c o m p l i c a t i o n s of D-penicillamine therapy. A reversible form of myasthenia gravis has been reported in E n g l a n d to be associated w i t h the use of D-penicillamine for the treatment of severe rheumatoid arthritis (4) and Wilson's D i s e a s e (5). This report describes the case of a patient w h o developed myasthenia gravis w h i l e being treated w i t h D-penicillamine for rheumatoid arthritis. A 40-year-old woman with ketosis-prone diabetes mellitus, rheumatic heart disease, and progressive rheumatoid arthritis since her teens, had been treated with conventional therapy and gold salts without improvement in her arthritic condition. She was begun on an increasing dose of D-penicillamine, 250 mg tablets, to a total of 1.5 g daily. After 2 months, the patient developed a decrease in the duration of her morning stiffness and joint pain and an increase in her daily activities. Her joints improved objectively. Laboratory tests showed that the erythrocyte-sedimentation rate had fallen from a high of 120 m m / h to a low of 22 m m / h , and the latex fixation titer, which had been as high as 1:2560, fell to a low of 1:10. After 4 months of treatment, she gave a 2-week history of a drooping left eyelid and diplopia. Neurologic examination showed a ptotic left eyelid with decreased range of motion of the left eye to upward and lateral gaze. The remainder of the neurologic exam was normal. The Tensilon® test was done with saline used as a control. After 2 mg of intravenous Tensilon the left eyelid became less ptotic. After a total of 10 mg intravenously, no ptosis could be detected and the extraocular muscles showed a full range of motion. Intravenous saline caused no change in the ptosis. Laboratory studies including thyroid function studies, antinuclear antibody, and antimitochondrial antibody, gave unremarkable findings. A chest roentgenogram did not show evidence of thymic enlargement. The D-penicillamine was withdrawn, and the patient was treated with pyridostigmine bromide (Mestinon®) with alleviation of the ptosis and diplopia. From September 1975 through March 1976 repeated attempts to wean her off Mestinon were unsuccessful, although the dosage was decreased. Finally, in April 1976 the Mestinon was stopped and neither the ptosis nor the diplopia occurred. In the 10 months since the Mestinon was withdrawn, the patient has not had a recurrence.
Bucknall and associates (4) reported four patients with rheumatoid arthritis who developed myasthenia gravis while taking D-penicillamine. In one patient, after withdrawal of the D-penicillamine, recovery occurred spontaneously in 2 weeks. In two of his four patients, pyridostigmine was initially required to control the myasthenic symptoms but was gradually reduced and eventually withdrawn without any recurrence of the myasthenia. In the fourth case, pyridostigmine was required in high dose, but the patient gradually improved and her requirements became less. In our patient the myasthenic symptoms did not develop for 5 months after initiation of Dpenicillamine, and 7 months of pyridostigmine therapy was needed to control the ptosis and diplopia. However, 10 months after cessation of pyridostigmine there has been no recurrence of the patient's symptoms. The myasthenic syndrome, occurring during treatment 578
November 1977 • Annals of Internal Medicine • Volume 87 • Number 5
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with D-penicillamine does not appear to be limited to patients with rheumatoid arthritis. Czlonkowska (5) reported one patient with Wilson's Disease who developed myasthenia gravis after 13 months of D-penicillamine therapy. The D-penicillamine was withdrawn, and after 6 weeks the patient showed no signs of myasthenia. The prevalence of myasthenia gravis in patients with rheumatoid arthritis is unknown but is apparently rare. Because of the reversibility of the myasthenia syndrome and its temporal relation to D-penicillamine therapy, we feel that the myasthenia gravis that developed in our patient was caused by D-penicillamine. The daily dosage of 1.5 g of D-penicillamine used in our patient was approximately twice the mean dosage currently recommended. Because D-Penicillamine has been reported to cause a reversible form of myasthenia gravis in Wilson's Disease, a nonimmunologic disorder, we believe that D-penicillamine does not act by "unmasking" these immune disorders in patients with an already altered immune system. Rather, D-penicillamine must cause these immunologic phenomena through an independent mechanism presently unexplained, which appears to be reversible. With the increasing use of D-penicillamine as a treatment of rheumatoid arthritis in the United States, this complication needs recognition. It is important to comply to recommended dosages because this complication may be dose-related. R O B E R T A. G O R D O N , M . D . J O H N W. B U R N S I D E , M.D., F.A.C.P.
Department of Medicine Division of Internal Medicine The Milton S. Hershey Medical Center The Pennsylvania State University Hershey, PA 17033 Received 18 April 1977. REFERENCES 1. C R O U Z E T J, C A M U S J P , L E C A A P , G U I L L I E N
P, L I E V R E JA: Lupus
induced by D-penicillamine during the treatment of rheumatoid arthritis. Ann Med Interne (Paris) 125:71-79, 1974 2. S T E R N L I E B
I, B E N N E T T B, SCHEINBERG
IH:
D-penicillamine-induced
Goodpasture's Syndrome in Wilson's Disease. Ann Intern Med 82:673675, 1975 3. CUCHER BG, G O L D M A N AL: D-penicillamine-induced polymyositis in rheumatoid arthritis. Ann Intern Med 85:615-616, 1976 4. B U C K N A L L R C , D I X O N AJ, G L I C K E N , W O O D W A R D J, Z U T S H I
DW:
Myasthenia gravis associated with penicillamine treatment for rheumatoid arthritis. Br Med J 1:600-603, 1975 5. CZLONKOWSKA A: Myasthenia syndrome during penicillamine treatment. Br Med 72:726-727, 1975
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Bucknall and associates (4) reported four patients with rheumatoid arthritis who developed myasthenia gravis while taking D-penicillamine. In one patient, after withdrawal of the D-penicillamine, recovery occurred spontaneously in 2 weeks. In two of his four patients, pyridostigmine was initially required to control the myasthenic symptoms but was gradually reduced and eventually withdrawn without any recurrence of the myasthenia. In the fourth case, pyridostigmine was required in high dose, but the patient gradually improved and her requirements became less. In our patient the myasthenic symptoms did not develop for 5 months after initiation of Dpenicillamine, and 7 months of pyridostigmine therapy was needed to control the ptosis and diplopia. However, 10 months after cessation of pyridostigmine there has been no recurrence of the patient's symptoms. The myasthenic syndrome, occurring during treatment 578
November 1977 • Annals of Internal Medicine • Volume 87 • Number 5
Downloaded from https://annals.org by Tulane University user on 01/14/2019
with D-penicillamine does not appear to be limited to patients with rheumatoid arthritis. Czlonkowska (5) reported one patient with Wilson's Disease who developed myasthenia gravis after 13 months of D-penicillamine therapy. The D-penicillamine was withdrawn, and after 6 weeks the patient showed no signs of myasthenia. The prevalence of myasthenia gravis in patients with rheumatoid arthritis is unknown but is apparently rare. Because of the reversibility of the myasthenia syndrome and its temporal relation to D-penicillamine therapy, we feel that the myasthenia gravis that developed in our patient was caused by D-penicillamine. The daily dosage of 1.5 g of D-penicillamine used in our patient was approximately twice the mean dosage currently recommended. Because D-Penicillamine has been reported to cause a reversible form of myasthenia gravis in Wilson's Disease, a nonimmunologic disorder, we believe that D-penicillamine does not act by "unmasking" these immune disorders in patients with an already altered immune system. Rather, D-penicillamine must cause these immunologic phenomena through an independent mechanism presently unexplained, which appears to be reversible. With the increasing use of D-penicillamine as a treatment of rheumatoid arthritis in the United States, this complication needs recognition. It is important to comply to recommended dosages because this complication may be dose-related. R O B E R T A. G O R D O N , M . D . J O H N W. B U R N S I D E , M.D., F.A.C.P.
Department of Medicine Division of Internal Medicine The Milton S. Hershey Medical Center The Pennsylvania State University Hershey, PA 17033 Received 18 April 1977. REFERENCES 1. C R O U Z E T J, C A M U S J P , L E C A A P , G U I L L I E N
P, L I E V R E JA: Lupus
induced by D-penicillamine during the treatment of rheumatoid arthritis. Ann Med Interne (Paris) 125:71-79, 1974 2. S T E R N L I E B
I, B E N N E T T B, SCHEINBERG
IH:
D-penicillamine-induced
Goodpasture's Syndrome in Wilson's Disease. Ann Intern Med 82:673675, 1975 3. CUCHER BG, G O L D M A N AL: D-penicillamine-induced polymyositis in rheumatoid arthritis. Ann Intern Med 85:615-616, 1976 4. B U C K N A L L R C , D I X O N AJ, G L I C K E N , W O O D W A R D J, Z U T S H I
DW:
Myasthenia gravis associated with penicillamine treatment for rheumatoid arthritis. Br Med J 1:600-603, 1975 5. CZLONKOWSKA A: Myasthenia syndrome during penicillamine treatment. Br Med 72:726-727, 1975
Brief Reports
Downloaded from https://annals.org by Tulane University user on 01/14/2019
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