Urokinase therapy in systemic sclerosis

INTRODUCTION. Systemic Sclerosis (SSd) is a very serious disease usually the prognosis remains very poor because of the involvement of visceral organs. Malignant ventricular arrthythmias, pulmonary fibrosis, renal insufficiency and malignant hypertension are a major cause of morbidity and mortality. Since vascular damage occurs typically in, vasoactive drugs are, usually, employed in the treatment of the disease but the prognosis remains therapeutically challenging at present. PATIENTS AND METHOD. We are treating with Urokinase-therapy 20 SSd patients(ps) aged between 33 and 72 years. The duration of the disease was 5 years or longer in 11 and shorter than 5 years in all the remaining ps. All but two showed Raynaudʹs phenomenon. Serum antinuclear antibodies (ANA) were positive in 15 ps; 7 ps had Anticentromere antibodies (ACA) and 2 ps anti-Scl 70 antibodies, too. Urokinase-therapy (uPA-t) is being given intravenously at a dose of 3000 IU/Kg/day in a 5% glucose solution for 7 days/every month for four months and then for 3 days/every month for the last months. Clinical evaluations (hand prints, clinical chemistry and immunological tests, capillaroscopy, ultrasonograph study of the skin, pulmonary function and kidney function) are performed both at baseline and every month. Echocardiogram has been scheduled every six months; skin biopsy and esophagram at the beginning and at the end of the study. 16 ps who carry, without changes, on their long-standing, stabilised treatment with Penicillamine (600 mg daily) are treated with placebo (5% glucose solution without uPA-t) and they represent the control-group. RESULTS. The ps on uPA-t show an objective significant improvement in skin ulcers and sclerosis. Capillaroscopy shows signs of re-vascularization and B-scan image of the skin shows a decrease echogenicity with reappearance of fine structural stippling of the epidermis and dermas. The uPA-t is well tolerated and no significant side effects were detected during the infusion or thereafter. CONCLUSIONS. We have found only one previous study with uPA-t for acute digital ischemia of SSd. The drug was administered for a short period only in two ps, in stepwise combination with neurol blockade and prostaglandin E1. The drug reduced the necrotic areas predicted before therapy and saved fingers from amputation. Our study is the first in which uPA-t was used for the systemic treatment of SSd in a large number of ps and for a prolonged period.