 |
|
 |
An infectious disease due to the fungus Cryptococcus neoformans (formerly known as Torula histolytica), with a primary focus in the lung and characteristic spread to the meninges and occasionally to the kidneys, bone, and skin. It is a defining disease for AIDS.
Etiology, Incidence, and Pathology
Distribution is worldwide. In the USA, more cases occur in men aged 40 to 60. Individuals with Hodgkin's disease are particularly susceptible.
CNS lesions include diffuse meningitis, meningeal granulomas, infarcts, areas of softening, increase in neuroglia, or extensive tissue destruction. Cutaneous lesions appear as acneiform pustules or granulating ulcers. Subcutaneous and visceral lesions are deep nodules or tumorlike masses filled with gelatinous material. Acute inflammation is minimal or absent, but infiltration with lymphocytes and fibroblasts, and with plasma, "foam," and giant cells, is seen occasionally.
Symptoms and Signs
In meningitis, headache is the most common symptom. The patient seeks medical care because of blurred vision or is brought to the physician because of such mental disturbances as confusion, depression, agitation, or inappropriate speech or dress. CSF examination shows elevated protein and cell count (mostly lymphocytes) in about 90% of patients, and decreased glucose in 50%; C. neoformans can be seen on microscopic examination of specimens prepared with India ink in 60% of patients, but antigen can be detected by latex agglutination test in >90%.
The infection is acquired via the respiratory route with a primary focus in the lung; more recently, a benign, rarely progressive, pulmonary form often accompanying other lung disease has been recognized. Cough or other pulmonary symptoms are usually present.
The kidney is the next most common organ involved. C. neoformans can be cultured from the urine in about 30% of patients with meningitis. Although renal infection is usually asymptomatic, pyelonephritis with renal papillary necrosis has been reported. In AIDS patients, a focus of persistent infection after primary treatment has been the prostate.
Skin lesions (pustules or ulcers) and bone lesions (osteomyelitis) are seen less frequently.
Diagnosis
Appearance of the budding yeast surrounded by a clear capsular area in sputum, pus, other exudates, or CSF with application of an India ink preparation strongly suggests the diagnosis. Similar encapsulated yeast forms, seen on proper staining of fixed tissues, are also almost diagnostic. The latex particle agglutination test for antigen is useful with CSF, blood, and urine. Culture and identification of the causative fungus confirm the diagnosis. The fungus is readily cultured from blood in AIDS patients.
Prognosis and Treatment
For meningitis, a combination of amphotericin B and flucytosine is best: amphotericin B IV 20 mg/day (or 0.3 mg/kg/day) and flucytosine orally 150 mg/kg/day in 4 equally divided doses, both for 6 wk. About 85% of non-AIDS patients respond to such antifungal treatment, but only 50% of AIDS patients respond, and those who do require continuous, probably lifelong, suppressive treatment. Fluconazole orally 200 mg/day has been shown to be effective and less toxic for such suppression than amphotericin B IV 1 mg/kg/wk.
Non-AIDS patients with nonprogressive pulmonary disease may need no treatment. Skin, bone, and renal infections require therapy, though these forms are intermediate in severity. Once sensitivity has been demonstrated, flucytosine orally 150 mg/kg/day q 6 h may be sufficient. Flucytosine is not metabolized and is excreted principally by the kidney. Renal and hematologic status should be determined before therapy, and the drug must be given with caution to patients with impaired renal function or bone marrow depression. Frequent (ie, twice weekly) monitoring of renal and hematologic function is essential throughout therapy to determine the interval between doses.
Adverse reactions include GI disturbances; rash; anemia; leukopenia; thrombocytopenia; occasionally, elevation of hepatic enzymes, BUN, and creatinine; and infrequently, confusion, hallucination, or headache. Leukopenia, thrombocytopenia, and occasionally, elevated AST (SGOT) levels have occurred, which can be caused by the drug, the underlying disease, the infection, or a combination of these factors.
|
 |
