Disseminated and Relapsing Cryptococcosis: What We Still Have to Learn—a Case Series and Review of Literature

Abstract

Two cases of disseminated cryptococcosis are described. The first was an HIV-infected patient where cryptococcosis was diagnosed as “unmasking immune reconstitution syndrome”; the second was an immunosuppressed patient with multiple myeloma. In both cases, a definitive healing could not be reached despite long therapeutic approaches. This review summarizes both the most recent and relevant studies about disseminated and refractory form of cryptococcal infections and identifies research gaps. Given the limited data, we draw some conclusions with respect to management from literature: not clear and accepted indication are available regarding disseminated cryptococcosis, no specific schemes were identified, and the duration of therapy is usually decided case by case and supported only by case reports. In this perspective, usually standard therapeutic schemes and duration of induction depend on multiple factors (e.g., neurologic deficit, non-HIV/non transplant status, CSF culture positivity at 2 weeks, etc.). We found that there are no empiric and literature data that support a role of cryptococcal serum antigen (CRAG) in guiding the antifungal therapy; with the data collected, we think that although is possible, it is very rare to find disseminated cryptococcosis with negative CRAG. We looked also for the more important risk factor of recurrence. Some possible causes explored are risk of azole resistant strains, pre-existent conditions of patients that play a permissive role and the common situation where flucytosine is unavailable that led to suboptimal induction phase of therapy. Herein, we discuss disseminated cryptococcosis with a particular attention to antifungal therapy, role of cryptococcal antigen, and risk factors for recurrence of disease.