Asymptomatic pulmonary cryptococcosis in solid organ transplantation: report of four cases and review of the literature.

Cryptococcus neoformans is the third most common cause of invasive fungal infections in solid organ transplantation. The infection generally presents as disseminated disease, involving multiple sites including the central nervous system, lungs, and skin. An increase in the incidence of primary pulmonary cryptococcal infections has been reported recently in solid organ recipients; these infections were generally symptomatic with an accelerated clinical course. We report four cases of asymptomatic pulmonary cryptococcosis in solid organ recipients (kidney, n=2, heart, n=2). In each case, an incidental finding on a routine chest radiograph led to the microbiological or histopathological diagnosis of invasive pulmonary C. neoformans infection. In these patients, cryptococcosis occurred a median of 25 months (range 7-36 months) after organ transplantation. All patients had a calcineurin inhibitor, prednisone, and azathioprine or mycophenolate mofetil as part of their immunosuppressive therapy at the time of diagnosis. Serum cryptococcal antigen was available and positive in the three patients studied; assessment of cerebrospinal fluid (CSF) of all four patients revealed no organisms by smear or culture. Therapy consisted of oral fluconazole in all cases, with flucytosine in one case, combined with resection of lung tissue in two individuals. All patients have remained free of cryptococcal disease (follow-up median 42 months, from 18 to 88 months). Cryptococcal disease in solid organ recipients may present as asymptomatic, localized pulmonary disease. The natural history of such infections is unknown. New pulmonary radiographic findings should prompt an aggressive diagnostic evaluation including serum and CSF cryptococcal antigen assays, and a biopsy of pulmonary lesions. Prolonged therapy may be used to reduce the risk of progression and dissemination during periods of intensified immune suppression.