Treatment of Patients with Thromboangiitis Obliterans with Cyclophosphamide

Abstract

This report describes a small, nonrandomized trial of cyclophosphamide in the treatment of patients with advanced thromboangiitis obliterans (TAO) with modest results. The rationale of the treatment was based on the immunopathogenesis of the disease, ie, autoimmune vasculitis of peripheral arteries. Twelve male patient volunteers with TAO were included for the trial. Diagnosis was based on the history of chronic smoking or tobacco chewing, clinical features of ischemia of peripheral vessels, radioarteriography showing arterial block, and characteristic histopathologic changes of affected arteries. Cyclophosphamide (400 mg) was given intra venously daily to the patients for 7 days followed by daily oral administration of 100 mg cyclophosphamide for another 7 weeks. Clinical conditions of the patients started to improve during the third week of the treatment and maximum benefit was noticed at the end of the treatment. There was significant decrease of intermittent claudication and twentyfold increase of claudication distance as well as relief of rest pain. Before starting treatment 6 patients had developed ulcers on their affected limbs; these healed completely in 2, partially healed in another 2, and showed no improvement in the remaining 2, who never stopped smoking. However, immunosuppressive therapy failed to show any improvement of arterial block, as evidenced by radioarteriography and any significant increase of skin temperature over the affected limbs. Nevertheless, histopathologic studies of biopsies taken from the diseased arteries after completion of therapy showed decreased influx of lymphocytes and plasma cells in the thrombi as well as in the arterial walls in comparison to the biopsies taken before the start of treatment. During the treatment the degree of immunosuppression was monitored by blood leukocyte and lymphocyte counts, which were kept between 4,000/mm3 and above 3,000/mm3 and not less than 500/mm 3, respectively, indicating modest immunosuppression and no serious complications. All patients were followed up for 1 year. Only 2 patients, who resumed smoking, had relapse.