Cryptococcal immune reconstitution inflammatory syndrome: report of four cases in three patients and review of the literature.

Immune reconstitution inflammatory syndromes (IRIS) in patients with AIDS are characterized by atypical manifestations of opportunistic pathogens in patients experiencing improvement in CD4 cell counts following receipt of highly active anti-retroviral therapy (HAART). We report four cases of IRIS due to Cryptococcus neoformans in three patients and review the literature of cryptococcal IRIS in AIDS (an additional 21 episodes). The IRIS presentation was lymphadenitis in all three patients; one patient also had meningeal IRIS. Combining our patients with the literature review revealed the following IRIS presentations: lymphadenitis (n=14), central nervous system (CNS) IRIS (n=10): meningitis in six and mass lesions in four, and pulmonary cavities (n=1). The median CD4 count of cases at the time of initial cryptococcal diagnosis and prior to the start of HAART was 25 cells/microl and the median HIV viral load was 439,053 copies/ml. At time of presentation of the IRIS, the median CD4 count had increased by 197 cells/microl. The median time from initial cryptococcal diagnosis and the start of HAART to the IRIS was 11 months (range 7 weeks to 3 years) and 7 months (range <2 weeks to 22 months), respectively. Patients with CNS IRIS tended to have shorter intervals from initiation of HAART to presentation compared to patients with lymphadenitis: median 3.5 months compared to 7 months. In 24 of 25 cases, the clinical manifestations of the IRIS resolved (range: days to months). Only four patients were given anti-inflammatory medications: corticosteroids in two and non-steroidal anti-inflammatory drugs in two, thus precluding assessment of efficacy. Patients with cryptococcal disease who initiate HAART are at risk for cryptococcal IRIS.