Chagas' disease reactivation after heart transplantation: Efficacy of allopurinol treatment

Background: Chagas' disease is a parasitic infection that provokes a severe form of dilated cardiomyopathy. In the initial experience with heart transplantation with Chagas' disease, a high rate of acute reactivation has been reported. Although benzinidazole and nifurtimox are effective in the treatment of reactivation or of the acute phase of the disease they ate associated with important adverse effects. Allopurinol has substantial activity against Trypanosoma cruzi in vitro, in the experimental laboratory and in chronic human Chagas' disease; however, there is no information regarding its action in Chagas' reactivation after heart transplantation.Methods and Results: We describe two patients with Chagas' disease who underwent heart transplantation. The first one had asthenia, anorexia, and several painful subcutaneous nodules in the legs after transplantation; biopsy showed an inflammatory infiltrate with intracytoplasmatic nests of Trypanosoma cruzi, confirmed by immunohistochemical stains with monoclonal antibodies specific to parasitic antigens. Allopurinol (600 mg/day) produced complete regression of the symptoms and the nodules with a negative control biopsy within 2 weeks. Treatment was maintained for 2 months. Mild leukopenia developed which improved after azathioprine reduction, and no further side-effects were noted. The second patient had sudden heart failure 6 months after transplantation; endomyocardial biopsy showed myocardial fibers infested with Trypanosoma, and a concomitantly performed right heart catheterization showed a low cardiac index and high filling pressures. The patient received allopurinol at a daily dose of 900 mg and conventional treatment for heart failure. Echocardiogram showed improved wall motion and decreased left ventricular dimensions, and control biopsy showed no inflammatory activity; cardiac index and filling pressures normalized. Treatment was maintained for 2 months without side effects. The two patients have not had recurrences and were in New York Heart Association functional class I 12 and 3 months, respectively, after discontinuation of allopurinol.Conclusions: Allopurinol seems to be safe and effective in treating Chagas' disease reactivation after heart transplantation. A larger number of case studies seems to be necessary to properly evaluate its role in the treatment of Chagas' disease reactivation.ESCOLA PAULISTA MED,DIV CARDIOL,SAO PAULO,BRAZILESCOLA PAULISTA MED,DIV CARDIOL,SAO PAULO,BRAZILWeb of Scienc

Schistosomal hepatopathy

Gross anatomical features and a complex set of vascular changes characterize schistosomal hepatopathy as a peculiar form of chronic liver disease, clinically known as "hepatosplenic schistosomiasis". It differs from hepatic cirrhosis, although clinical and pathological aspects may sometimes induce confusion between these two conditions. Intrahepatic portal vein obstruction and compensatory arterial hypertrophy render the hepatic parenchyma vulnerable to ischemic insult. This may lead to focal necrosis, which may give place to focal post-necrotic scars. These events are of paramount importance for the clinico-pathological evolution of schistosomal hepatopathy. Although portal fibrosis due to schistosomiasis sometimes reveals numerous myofibroblasts, it does not mean that such fibrosis belongs to a peculiar type. Damage to the muscular walls of the portal vein may be followed by dissociation of smooth muscle cells and their transition toward myofibroblasts, which appear only as transient cells in schistosomal portal fibrosis. Studies made with plastic vascular casts, especially those with the murine model of "pipestem" fibrosis have helped to reveal the mechanisms involved in systematized portal fibrosis formation. However, the factors involved in the pathogenesis of hepatosplenic disease remain poorly understood. A process of chronic hepatitis is a common accompaniment of portal fibrosis in schistosomiasis. Most of the times it is caused by concomitant viral infection. However, no especial interaction seems to exist between schistosomal hepatopathy and viral hepatitis