Intravenous cyclophosphamide pulse therapy for the treatment of lung disease associated with scleroderma

Until recently, renal crisis was the most significant cause of morbidity an d mortality in patients with scleroderma (SSc). Nowadays, following the int roduction of angiotensin-converting enzyme inhibitors used in renovascular hypertension, pulmonary fibrosis and pulmonary hypertension have become the most common causes of death in SSc. Consequently, the early diagnosis and treatment of pulmonary fibrosis is essential to improve morbidity and morta lity in SSc patients. The aim of this study was to investigate the effect o f intravenous cyclophoshamide pulse therapy in patients with SSc and eviden ce of active alveolitis assessed on a high resolution computed tomographic (HRCT) scan, and to compare the effect of cyclophosphamide pulse therapy wi th oral therapy. Sixteen consecutive patients with SSc were allocated alter nately to the two treatment groups. Eight patients were treated with monthl y cyclophoshamide pulse therapy (750 mg/m(2)) for 12 months; the other eigh t patients were treated with oral cyclophosphamide (2-2.5 mg/kg/day) for th e same period. All patients received concurrently prednisone (10 mg/day). P ulmonary function tests and HRCT scans were performed before therapy and at 6 and 12 months. In the oral cyclophosphamide group, three patients with a grade I pattern showed regression of disease extent. In the other five pat ients tone with grade LI and four with grade III) the pattern and extent of disease remained stable during the study. No statistical differences were found in forced expiratory volume in 1 s, forced vital capacity and total l ung capacity during the study period. The diffusing capacity for carbon mon oxide increased significantly between baseline and 12 months (p = 0.043). I n the cyclophosphamide pulse therapy group, seven patients with a grade I p attern showed regression of disease extent at 6 months (p = 0.018) and 12 m onths (p = 0.012). One patient with grade III remained stable during the st udy. In both groups the regression of the extent of disease estimated on HR CT was due to a decrease in the ground glass appearance. The extent of the reticular appearance remained stable throughout the study. Our results indi cate that cyclophosphamide pulse therapy is effective in suppressing active alveolitis (ground glass appearance). Although in this study it is not pos sible to compare pulse therapy with oral therapy because of the different p attern seen on HRCT between the two groups, it seems that oral therapy is a lso effective in suppressing active alveolitis. Neither regimen improved pu lmonary involvement when the reticular appearance predominated over the gro und glass appearance on HRCT. It is concluded that either pulse or oral cyc lophosphamide therapy may improve the outcome of SSc patients.