D-penicillamine induced myasthenia gravis in rheumatoid arthritis: An unpredictable common occurrence?

Summary Five patients out of 71 with rheumatoid arthritis (RA), who received D-penicillamine, developed myasthenia gravis (MG) within a two-year period. They all responded promptly to discontinuation of the drug and pyridostigmine administration. None of the patients had anti-Ro(SSA) antibodies or features of Sjögren's syndrome, whereas three of the five had the HLA-DR₁ phenotype. The relatively high frequency of MG observed in our population, along with its unpredictability and potentially serious sequelae, necessitates its inclusion in the list of side effects of D-penicillamine routinely discussed with the patient, prior to initiation of the treatment. Full alertness of both the patient and the physician to even minor initial myasthenic symptoms, that dictate immediate discontinuation of the drug, is of obvious importance.     

Progressive proliferative glomerulonephritis in a patient with rheumatoid arthritis treated with D-penicillamine.

A 49 year old man with rheumatoid arthritis developed a proliferative glomerulonephritis with progressive renal impairment during treatment with D-penicillamine. His renal function continued to deteriorate after the drug was stopped but improved after treatment with corticosteroids and azathioprine.     

Etanercept induced organizing pneumonia in a patient with rheumatoid arthritis

TNF inhibitors are being used in a rapidly expanding number of rheumatoid arthritis (RA) patients due to their effectiveness and acceptable safety profiles. To date, concerns regarding the adverse effects of TNF inhibitors have focused on infections, hematologic malignancies, and demyelinating disorders. Recently, the development of autoantibodies and other autoimmunity has been increasingly reported. Here, we describe a 36-year-old RA patient in whom organizing pneumonia and systemic lupus erythematosus were detected during etanercept treatment.     

D-penicillamine and gold salt treatments were complicated by myasthenia and pemphigus,respectively, in the same patient with rheumatoid arthritis

A 53-year-old woman with rheumatoid arthritis developed myasthenia gravis after 6 months of therapy with D-penicillamine. Nineteen months after D-penicillamine was discontinued and 12 months after the beginning of gold therapy, she developed pemphigus vulgaris. This is the first reported case of gold-induced pemphigus in rheumatoid arthritis. This study further underlines the complex interactions between the effects of treatment with sulfhydryl-disulfide exchange drugs and the altered immunological system of patients affected by rheumatoid arthritis.     

Fatal Strongyloides hyper-infection in a patient with myasthenia gravis

Purpose

We report a fatal case of Strongyloides hyper-infection as the result of corticosteroid therapy of a patient with myasthenia gravis.

Case presentation

Our patient was a farmer with a past history of living in an endemic area for Strongyloides stercoralis in Iran. Hyper-infection was diagnosed during the advanced-stage disease by demonstration of enormous number of larvae in the direct smears prepared from both the stool and tracheal secretions. Unfortunately, despite appropriate anti-parasite therapy, the patient died due to respiratory failure.

Conclusion

We recommend the provision of more awareness in high-risk people prior to immunosuppressive therapy, through screening for S. stercoralis, even in non-endemic regions.     

D-penicillamine withdrawal in rheumatoid arthritis.

Thirty-eight patients with rheumatoid arthritis in remission on penicillamine were entered into a prospective, randomised, placebo controlled study to determine the effects of gradual penicillamine withdrawal, to find a serological marker capable of predicting relapse, and to assess the effects of reintroduction of penicillamine. 80% of patients attempting gradual penicillamine withdrawal flared. There was no single serological marker capable of predicting outcome consistently. Decreasing SH levels were highly specific for recurrence of active synovitis but were insensitive. Reintroduction of penicillamine was successful. The implications of these findings, particularly concerning duration of therapy with disease modifying drugs, are discussed.     

A case of rheumatoid arthritis with bucillamine-induced myasthenia gravis treated by immunoadsorption therapy]

We report a case of 48-year old female with rheumatoid arthritis (RA) complicated with myasthenia gravis. In 1988, she was diagnosed of having RA, and several therapeutic drugs were administered, but her disease activity was in poor control. In July 1993, bucillamine (BU) was started at a dose of 100 mg/day, and her arthritis subsided. However, in October 1996, she was admitted with a rapidly progressive ptosis and double vision in the left eye, which became prominent in the evening. Because serum concentration of the antibody to acetylcholine receptors (AchR Ab) was elevated at 12.6 nmol/l, and the ptosis was reversed immediately after a tensilon test, ocular type myasthenia gravis (MG) was diagnosed and it was thought to have been induced by BU. Immunoadsorption therapy was started after discontinuation of this drug, and was continued for 6 months, resulting in improvement of neurological symptoms and decrease in AchR Ab level. MG has not recurred since. Although several cases of D-penicillamine (DP) induced MG are reported, only two cases are reported which were induced by BU, sulfhydryl compound which has a structure similar to DP. Since BU has been widely used as one of the disease modifying anti-rheumatic drugs in Japan, MG induced by this drug should be paid attention as one of the adverse effects.     

Leukoencephalopathy induced by low-dose methotrexate in a patient with rheumatoid arthritis

We report a patient with rheumatoid arthritis (RA) who developed leukoencephalopathy while being treated with low-dose methotrexate (MTX). She suddenly developed loss of recent memory and left homonymous hemianopsia ascribable to the bilateral but right-predominant occipitotemporal lesions. Intravenous administration of dexamethasone and cessation of MTX quickly relieved her clinical symptoms. Low-dose MTX-induced leukoencephalopathy is a rare complication in RA, but is important with regard to the possibility of serious neurological sequellae.     

HLA-DR antigens and proteinuria induced by aurothioglucose and D-penicillamine in patients with rheumatoid arthritis

By means of a case-control study we investigated the association between HLA phenotypes and the development of proteinuria after aurothioglucose or D-penicillamine treatment in patients with rheumatoid arthritis (RA). HLA-DR3 was markedly increased in 44 treatment cases compared with 66 RA controls (46 versus 18%, p = 0.002). HLA-DR3 positive patients were at greater risk during treatment with D-penicillamine (RR 10.1, p = 0.001) than gold treated cases (RR 1.7, p = 0.365). The associations between HLA-DR3 and nephrotic syndrome (RR = 6.3, p = 0.004) and early onset proteinuria (RR = 5.4, p less than 0.001) were stronger compared with uncomplicated proteinuria (RR = 3.1, p = 0.017) and late-onset proteinuria (RR = 1.6, p = 0.459), respectively. It appears that genetic factors in RA influence the development, the degree and the time of onset of drug induced proteinuria.     

Autoantibody to growth hormone in a patient with myasthenia gravis

An autoantibody to GH was detected in the serum from a patient with myasthenia gravis (MG) who had never been prescribed GH. Using an immunoprecipitation technique, this autoantibody was found to belong to the IgG class and had a kappa chain. The dissociation constant of the antibody was 56.8 nmol/l and the binding capacity was 37 nmol/l. Serum samples from another 130 patients, including 37 with MG, were examined, but the GH autoantibody could not be detected. To our knowledge, this is the first report demonstrating the presence of a GH autoantibody.     

D-penicillamine in the treatment of rheumatoid arthritis

Forty-four patients with definite or classic rheumatoid arthritis and failure to tolerate or respond to gold therapy were treated with D-penicillamine on a so-called go-slow, go-low regime. Seventeen patients tolerated the drug and had a 3−13 month follow-up assessment; 8 were markedly improved, 6 moderately or slightly improved, and 3 unimproved. Penicillamine had to be discontinued in 9 patients because of toxic side effects.     

Facial muscular atrophy in a myasthenia gravis patient

A 56-year-old man with anti-acetylcholine receptor antibody-mediated myasthenia gravis had bilateral facial muscular atrophy and had noticed blepharoptosis 15 years earlier. From 45 to 51 years of age, 5-10 mg prednisolone and 180 mg pyridostigmine daily relieved his symptoms. Subsequently, these treatments no longer improved the facial weakness, though blepharoptosis was absent. At 56 years of age, the edrophonium test and repetitive supramaximal stimulation testing of the orbicularis oris were negative. Frontalis muscle needle electromyography showed low amplitude polyphasic units and an incomplete interference pattern. Facial muscle atrophy, caused by disuse atrophy from neuromuscular junction depletion, contributed to this patient's facial weakness.