HLA antigens and toxic reactions to sodium aurothiopropanol sulphonate and D-penicillamine in patients with rheumatoid arthritis.

One hundred and forty-one patients with rheumatoid arthritis treated with aurothiopropanol sulphonate or D-penicillamine, or both were examined for HLA antigens to investigate the genetic influence on the occurrence of different adverse reactions during therapy. All 13 patients possessing HLA-DR3 had toxic reactions. The relative risk for DR3 positives of developing skin eruptions or proteinuria was calculated to be 10.5 times and seven times respectively that of DR3 negatives. The incidence of DR7 antigen in 94 patients with toxic reactions was significantly decreased (11% compared with 28% in controls) suggesting a protective role for this antigen.     

Morphea-like reaction to D-penicillamine therapy.

We report the case of a 48-year-old woman who developed morphea-like plaques after 1 year of treatment with D-penicillamine at 250 mg daily for a seronegative erosive arthritis of rheumatoid type. The rash began as several red itchy patches on the trunk; these became thickened and shiny over about 3 months. The histological appearance was of increased dermal fibrosis with an inflammatory infiltrate round dermal capillaries. However, epidermal changes were not typical of morphea. New lesions ceased to appear within a few months of stopping penicillamine, and by 1 year all the plaques were pale and symptomless.     

Prior gold therapy does not influence the adverse effects of D-penicillamine in rheumatoid arthritis

One hundred fourteen patients with definite or classic rheumatoid arthritis were followed prospectively between January 1976 and April 1981 to monitor their toxicity pattern to D-penicillamine. The influence of previous sodium aurothiomalate therapy on the toxicity pattern of D-penicillamine is described. There was no significant difference in overall outcome of the patients treated with D-penicillamine with respect to adverse effects, whether they had previous gold toxicity, previous gold therapy but no toxicity, or no previous gold therapy. The time from gold toxicity to the start of D-penicillamine therapy was greater in those who did not develop D-penicillamine toxicity compared with those who did. This difference just reached statistical significance. Total gold salt received had no effect on eventual outcome of D-penicillamine treatment, and the toxicity pattern of D-penicillamine in those patients who had previous gold therapy was similar to those patients who had never received gold therapy.     

Zinc sulphate therapy for Wilson's disease after acute deterioration during treatment with low-dose D-penicillamine

A 30-year-old woman with Wilson's disease was treated with low-dose D-penicillamine. After 12 days, treatment was changed to zinc sulphate because of severe neurological deterioration. The patient subsequently improved within a few days. During a follow-up period of 20 months, the effectiveness of therapy was evaluated by measuring copper and zinc levels in plasma and urine, and by 64Cu-loading tests. We conclude that sulphate therapy may be a satisfactory alternative, even when rapid deterioration occurs in the early stages of D-penicillamine treatment.     

Prediction of progressive joint damage in patients with rheumatoid arthritis receiving gold or D-penicillamine therapy.

Seventy two patients with classical or definite rheumatoid arthritis (RA) were randomly allocated to receive gold or D-penicillamine therapy (DPA) in a prospective study designed to evaluate whether it is possible to predict which patients will show radiological progression despite therapy. Forty five patients completed 12 months' treatment. There were no significant demographic or clinical differences between them and the 27 drop outs. Twenty of the 45 patients showed no radiological progression between six and 12 months. These patients had less severe initial radiological damage, lower levels of serum aspartate transaminase (serum AST) and lactic dehydrogenase (LDH), but higher levels of serum cholesterol. Twenty five patients did show progression during the six to 12 month period. This group included all the men with nodules. Of the 43 pretreatment clinical and laboratory variables examined, however, the majority failed to predict whether or not progression would subsequently occur. This included the acute phase response and seropositivity.     

HLA system and side effects of gold salts and D-penicillamine treatment of rheumatoid arthritis.

Among 67 patients with rheumatoid arthritis treated with gold salts (aurothiopropanol sulphonate) a significant correlation (p less than 10(-2)) was noted between gold toxic reactions, whatever their type, and the HLA antigens A1, B8, Cw7, and DR3. Forty-two patients were genotyped, and a correlation was observed between gold side effects and the haplotype A1 Cw7 B8 DR3 (p less than 10(-2), RR = 8.0). In addition 3 out of 4 cases of renal intolerance to D-penicillamine were observed in patients possessing the Cw7 B8 DR3 haplotype.     

Erythropoietin as an adjunctive treatment for methanol-induced toxic optic neuropathy

Background: Methanol-induced optic neuropathy (MTON) is frequently seen in countries where alcohol consumption is banned or poorly regulated. MTON frequently results in blindness and there is no empirically validated treatment. Objective: To evaluate the effect of erythropoietin (EPO) as an adjunctive treatment for MTON. Methods: In this nonrandomized interventional comparative study, all participants were diagnosed with MTON and received the steroid methylprednisolone. Eleven participants received intravenous EPO (10000 IU twice a day) for three days as an adjuvant to methylprednisolone (EPO group); 11 participants in a historical control group received methylprednisolone only (control group). Main outcomes were best-corrected visual acuity (BCVA), peripapillary retinal nerve fiber layer thickness (PRNFLT), and visual field mean deviation (MD). Results: Mean BCVA improved significantly in both groups: from 2.93 ± 0.55 to 1.75 ± 1.16 LogMAR at month 3 (p < 0.001) in the EPO group, and from 2.65 ± 0.68 to 2.19 ± 0.75 at final visit in the control group (p = 0.001). The final BCVA was significantly better in the EPO group (p = 0.012). The mean PRNFLT decreased in both groups. However, at the final follow-up, PRNFLT was significantly thinner in the control group (53 ± 6 vs. 77 ± 26 microns, respectively; p < 0.001). Conclusion: Intravenous EPO plus high-dose intravenous steroid may be an effective combination therapy for the patients with MTON.     

Immunosuppression as initial treatment for gold induced aplastic anemia

Three patients who received antithymocyte globulin therapy for severe aplastic anemia due to gold therapy are described. In 2 patients the hemoglobin, white blood cell count and neutrophils were normal and platelet counts exceeded 100 X 10(9)/1 more than 2 years after treatment. The 3rd patient did not respond to antithymocyte globulin or to cyclosporine therapy; subsequent allogeneic bone marrow transplantation resulted in satisfactory engraftment at 12 months. In all 3 patients the arthritis was improved after the episode of marrow aplasia and its treatment. Including these 3 patients, 12 reported patients with severe aplastic anemia due to gold have now been treated with antithymocyte globulin; 8 have shown significant improvement. These results are better than those reported for any other treatment. Antithymocyte globulin may be optimal initial treatment for this serious disorder.