Bucillamine-induced Nephropathy / 대한류마티스학회지

OBJECTIVE: Bucillamine is a disease-modifying antirheumatic drug that's widely used in Korea and Japan, and it is reported to be a cause of proteinuria. However, the clinical course of the nephropathy associated with the use of bucillamine in rheumatoid arthritis patients has not been described in detail in Korea. METHODS: We examined clinical records of 835 patients who were treated with bucillamine for rheumatoid arthritis at least 2 months at Ajou University Hospital from 2003 to 2008, and we found 23 patients (2.75%) with proteinuria. Each patient was followed up until the proteinuria had resolved. RESULTS: At the time the proteinuria developed, the mean age of patients was 53.8+/-11.0 years. Only one patient had marked hypoalbuminemia (<3.0 g/dL). The mean value of the random urine protein-creatinine ratio was 3.44+/-2.99. The proteinuria appeared 4~18 months after the initiation of the treatment with bucillamine. Among the patients, renal biopsy was carried out in 18 patients, and pathological findings were 17 cases of membranous glomerulopathy and 1 case of focal segmental glomerulosclerosis. On the follow-up of the 18 patients, the proteinuria in all the patients had resolved completely without deterioration of renal function. But the time to resolution of the proteinuria was positively correlated with the length of bucillamine treatment after the onset of proteinuria (p<0.001, r=0.744). CONCLUSION: Prevalence of proteinuria in patients receiving bucillamine was 2.75%, and bucillamine-induced nephropathy showed a good prognosis in Korea. The most important thing for resolving the bucillamine-induced proteinuria is to discontinue the bucillamine.

Bucillamine-Induced Pemphigus Vulgaris in a Patient with Rheumatoid Arthritis and Polymyositis Overlap Syndrome

Bucillamine is a disease modifying anti-rheumatic drug, structurally similar to D-penicillamine. Although D-penicillamine-induced pemphigus has been not infrequently demonstrated, pemphigus associated with bucillamine was rarely reported. We describe a patient complicating pemphigus vulgaris after bucillamine treatment in rheumatoid arthritis (RA) and polymyositis (PM) overlap syndrome. PM and RA overlap syndrome was diagnosed three years ago and bucillamine was administrated for 20 months. Skin lesions including erythematous flaccid blisters on her chest, axillae, and back were occurred and were compatible with pemphigus vulgaris by typical pathology. Withdrawal from bucillamine and prednisolone treatment made rapid improvement of pemphigus lesions.

Effects of N-(2-mercapto-2-methylpropanoy1)-L-Cysteine(bucillamine) on the Activation of Nuclear Factor kB induced by TNF-a in Synovial Cells from Patients with Rheumatoid Arthritis / 대한류마티스학회지

No abstract available.

Effect of Intermittent Cyclic Etidronate Treatment on Bone Mineral Density of Postmenopausal Osteoporosis: Comparison with Continuous Estrogen Therapy / 대한류마티스학회지

No abstract available.

The Effect of Bucillamine in the Initial Treatment of Rheumatoid Arthritis and Treatment of Patients with Refractory Rheumatoid Arthritis / 대한류마티스학회지

OBJECTIVE: To assess the clinical effect of bucillamine in rheumatoid arthritis (RA), we performed an open clinical trial for 3 months. METHODS: 10 out of 12 patients completed bucillamine trial(200mg/day) for their initial treatment against arthritis, and 9 out of 11 patients with refractory RA completed the bucillamine trial. Disease activity was assessed by the duration of morning stiffness(MS), visual analogue pain scale(VAPS), functional capacity(FC), tender joint counts(TJC), swollen joint counts(SJC), ESR, and CRP every month. Adverse effects were monitored monthly. RESULTS: At the end of trial, all parameters were decreased in the initial treatment group except of CRP. No parameters were decreased in the refractory group. Gastrointestinal disturbance was the most commmon adverse effect. Skin rash, stomatitis, proteiuria and elevated hepatic enzyme were minor adverse effects. CONCLUSION: Bucillamine was effective in the initial treatment of rheumatoid arthritis, but not effective in the patients with refractory rheumatoid arthritis. Bucillamine is relatively safe in the treatment of rheumatoid arthritis in both groups.

Effects of Bucillamine on the Function of Human B Cell and T Cell / 대한류마티스학회지

OBJECTIVE: Bucillamine[N- (2-mercapto-2-methylpropionyl)-L-cysteine] (BUC) is a thiol compound that differs from D-pencillamine(DPC) in that it contains two free sulfhydryl groups. Clinical trials have suggested that the efficacy of BUC in rheumatoid arthritis(RA) is as effective as DPC, but the mechanism of action remains unclear. We therefore examined the effects of BUC on the in vitro function of human B cell and T cell in comparision to those of DPC. METHODS: The effect of BUC and DPC on Staphylococcus aureus Cowan 1 (SAC) induced IgM production by B cells from 11 healthy donors was examined. Phytohemagglutinin (PHA) induced proliferation and Interferon-r(IFN-r) and Interleukin-2 (IL-2) production by T cells was also examined. RESULTS: BUC and BUC-ID(SA981) suppressed the production of IgM at concentration of 0. 1-100 ug/ml, whereas DPC suppressed at concentration of 100 ug/ml. BUC and DPC inhibited PHA induced DNA synthesis of peripheral blood mononuclear cells(PBMCs) and T cell in a dose-dependent manner. DPC (10 ug/ml) significantly suppresed IFN-r production by PHA-stimulated T cells, but not suppressed IL-2 production, whereas BUC(10 ug/ml) not significantly suppressed IFN-r and IL-2 production. CONCLUSION: BUC has immunosuppressive effects inhibiting the function of B cells and T cell proliferation, whereas the action of DPC is targeted at T lymphocytes. BUC may be effective in rheumatoid factor positive RA patients who have not responded to treatment with DPC.

The Effect of Bucillamine of Trace Element Levels of Hair in Patients with Rheumatoid Arthritis / 대한류마티스학회지

OBJECTIVES: We investigated the changes of trace element levels in hair of patients with rheumatoid arthritis after bucillamine treatment. METHODS: We performed inductively coupled plasma atomic emission spectrometry in determination of trace element levels in hair of patients with rheumatoid arthritis. RESULTS: The results were as follows: 1) There was a significant increase of copper concentration, but no change in zinc level after bucillamine treatment. 2) There were no significant changes in copper and zinc concentrations between the proximal and distal portions of hair after long-term bucillamine treatment. CONCLUSIONS: Our results showed the significant increase of copper level and no significant change of zinc level in hair after bucillamine treatment, but, although statistically not significant, copper and zinc levels were decreased on experiment with divided hair. So, our findings do not permit any conclusion on the influence of bucillamine on trace element levels in hair. Further studies in large samples and comparison with the effect of D-penicillamine will be necessary to clarify the association of trace element levels in hair of rheumatoid arthritis patients and bucillamine treatment.

A Comparision Between Bucillamine And D-Penicillamine In The Treatmnt Of Rheumatoid Arthritis / 대한류마티스학회지

OBJECTIVE: In order to compare the clinical effect and frequency of side effects between d-penicillamine and bucillamine, a chemical derivative of d-penicillamine, we conducted a randomized, controlled clinical trial. METHODS: 22 and 24 patients were allocated in each treatment arm, after stratification according to functional class, anatomical stage, and concomittant steroid use. We evaluated tender joint count, swollen joint count, tenderness score, duration of morning stiffness, and grip strength every 4 weeks. Westergren ESR, hemoglobin, leucocyte and platelet count were also checked every 4 weeks, and C-reactive protein(CRP)quantitation and rheumatoid factor(RF) titration were checked at baseline and 16 weeks. Study period spanned 16 weeks. RESULTS: At the end of the trial, both swollen joint count and tenderness score decreased significantly from baseline in both groups, whereas tender joint count decreased siginficantly in bucillamine-treated group only. Grip strength also improved significantly in bucillamine group. Duration of morning stiffness decreased in both groups. When we arbitrarily defined response as more than 30% decrease in both tender and swollen joint count from baseline, 27% of bucillamine group and 33% of d-penicillamine group responded. The response rate did not differ significantly between the 2 groups. ESR and RF decreased in both groups, whereas CRP decreased significantly only in bucillamine group. The frequency of side effects lasting more than 1 day and possibly related to drug was 14% and 37% in bucillamine and d-penicillamine group, respectively. The difference was statistically not significant. CONCLUSIONS: Bucillamine is as effective as d-penicillamine in the treatment of rheumatoid arthritis. The frequency of side effect tended to be lower.