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Effect of d-penicillamine on pulmonary fibrosis in patients with systemic sclerosis
  1. M Jinnin,
  2. H Ihn,
  3. Y Asano,
  4. K Yamane,
  5. N Yazawa,
  6. K Tamaki
  1. Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113-8655, Japan
  1. Correspondence to:
    Dr H Ihn;

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It has been shown by some researchers that d-penicillamine stabilises or even improves pulmonary fibrosis in systemic sclerosis (SSc), and has a beneficial effect on patient survival,1,2 but this has been questioned by others.3–5 These controversial results from previous uncontrolled studies were due to short term treatment, absence of control subjects, small number of patients, or the lack of objective criteria for the determination of improvement or deterioration. In this report, we describe a retrospective study of the effect of d-Pen treatment in 65 Japanese patients.


Thirty nine patients with diffuse cutaneous SSc (dcSSc) and 26 with limited cutaneous SSc (lcSSc)6 with pulmonary fibrosis were randomly enrolled in this study (table 1). None of the patients had received any treatment by their first visit, and had taken no drugs which might affect pulmonary disease, except for d-Pen (100–600 mg/day) and corticosteroid during the follow up period. The percentage predicted vital capacity (%VC) and percentage predicted carbon monoxide transfer factor (%Tlco) were measured by pulmonary function test. Chest computed tomography (CT) or chest x ray examination was used for the evaluation of alveolitis or fibrosis.

Table 1

Patients characteristics. Values means (SD) if not indicated

The change in pulmonary fibrosis was evaluated for the patients with d-Pen treatment and those without during the follow up period, by measuring six variables; average of the changes in %VC or %Tlco levels of each patient (%VC or %Tlco levels before treatment minus those after treatment), prevalence of patients with over 5% reduction of %VC or %Tlco levels during the follow up period, and prevalence of patients with progression of alveolitis or fibrosis in chest CT or x ray examination during the follow up period. We also evaluated the interaction between d-Pen and each of the following factors: (a) extent of skin involvement (diffuse/limited) (b) duration of disease at the first visit (over/under 10 years); (c) duration of d-Pen treatment (over/under 3 years), and (d) taking corticosteroid treatment (+/−).

Statistical analysis was carried out with a Student’s t test for the comparison of means, and Fisher’s exact probability test for the analysis of frequency. The interaction of two factors was examined using two factor factorial analysis of variance. Values of p<0.05 were considered significant.


Table 2 shows the correlation between treatment with d-Pen and each of the six variables. No significant differences in the changes of these variables were found between the patients with d-Pen treatment and those without.

Table 2

The influence of d-penicillamine on pulmonary fibrosis. Values are means (SD) if not indicated.

Table 3 shows the interaction between d-Pen treatment and four factors described above. For example, table 3 shows that over 5% reduction of %VC was detected significantly more often in the patients with dcSSc than in those with lcSSc, but there was no interaction between d-Pen treatment and extent of skin involvement. This indicates that pulmonary disease in patients with dcSSc has higher tendency to progress than in patients with lcSSc, but the effects of d-Pen treatment did not differ between patients with dcSSc and those with lcSSc. Finally, there was no interaction between d-Pen treatment and each factor.

Table 3

Interaction between d-penicillamine treatment and extent of skin involvement (diffuse/limited), duration of onset—first visit (over/under 10 years), duration of d-Pen treatment (over/under 3 years), or corticosteroid treatment. Results are p values

Furthermore, we analysed 25 patients with d-Pen, to evaluate the association of dose of d-Pen treatment with each variable, but the change in pulmonary fibrosis did not depend on the dose of d-Pen (data not shown). Thus, in our study, we could not show any beneficial effect of d-Pen on pulmonary fibrosis.

But, our results had some limitations. We did not evaluate other manifestations, including the skin or kidney, in this study. And our results were obtained retrospectively. Future controlled trials of this drug should be performed with randomisation in various manifestations of this disease.


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