USMLE – Cryptococcosis
Cryptococcus neoformans is an encapsulated yeast that can cause meningoencephalitis in normal individuals but more frequently in patients with AIDS, leukemia, lymphoma, systemic lupus erythematosus, Hodgkin disease, or sarcoidosis and in transplant recipients. Many of these patients receive high-dose corticosteroids, a major risk factor for Cryptococcus infection.
C. neoformans is present in the soil and in bird (particularly pigeon) droppings and infects patients when it is inhaled. Three properties of C. neoformans are associated with virulence: (1) the capsular polysaccharide, a surface molecule that stains bright red with mucicarmine in tissues, stains negative in India ink preparations in CSF, and can be detected with antibody-coated beads in the CSF; (2) resistance to killing by alveolar macrophages; and (3) production of phenol oxidase; this enzyme consumes host epinephrine in the synthesis of fungal melanin, thus protecting the fungi from the epinephrine oxidative system present in the host nervous system. One reason that C. neoformans preferentially infects the brain may be that the CSF lacks alternative pathway complement components (present in serum) that bind to the carbohydrate capsule and facilitate phagocytosis and killing by polymorphonuclear cells.
Although the lung is the primary site of localization, pulmonary infection with C. neoformans is usually mild and asymptomatic, even while the fungus is spreading to the central nervous system. C. neoformans, however, may form a solitary pulmonary granuloma similar to the coin lesions caused by Histoplasma. The major pathologic change of C. neoformans is in the central nervous system, including the meninges, cortical gray matter, and basal nuclei. The tissue response to cryptococci is extremely variable. In immunosuppressed patients, organisms may evoke virtually no inflammatory reaction, so gelatinous masses of fungi grow in the meninges or in small cysts within the gray matter (soap-bubble lesions) as though in a culture medium. In nonimmunosuppressed patients or in those with protracted disease, the fungi induce a chronic granulomatous reaction composed of macrophages, lymphocytes, and foreign body type giant cells. Neutrophils and suppuration may also occur, as well as a rare granulomatous arteritis of the circle of Willis. In severely immunosuppressed persons, C. neoformans may disseminate widely to the skin, liver, spleen, adrenals, and bones.