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Cryptococcosis in the Non-HIV Patient. Kristen Amann, MD Morning Report August 12, 2009. Brief Overview. Yeast-like fungus Most common predisposing factor: HIV Usually CD 4 <200/ L Pathogenesis: Not entirely clear Likely inhalation Rare: cutaneous entry from minor trauma
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Cryptococcosis in the Non-HIV Patient Kristen Amann, MD Morning Report August 12, 2009
Brief Overview • Yeast-like fungus • Most common predisposing factor: HIV • Usually CD4 <200/L • Pathogenesis: Not entirely clear • Likely inhalation • Rare: cutaneous entry from minor trauma • Non-HIV associated: • 50%: glucocorticoids, immunosuppression • Remainder: transplant, lymphoma, sarcoidosis, idiopathic CD4 lymphocytopenia
Clinical Presentation • Most common presentation at the time of diagnosis is meningoencephalitis • Fatal without treatment • Early: headache, nausea, confusion, irritability, confusion • Fever and nuchal rigidity are mild to lacking • Progression: deep coma, brainstem compression • Neuroimaging: usually normal • Cryptococcomas
Clinical Presentation • Pulmonary cryptococcosis • Chest pain (40%), cough (20%), +/- fever • Cutaneous lesions • One to a few papules that enlarge slowly, develop central ulceration or softening
Diagnosis • CSF • glucose, protein • Lymphocytic pleocytosis • 90% will have a positive Ag in CSF or serum • Poor prognostic indicators • WBC < 10/µL • OP >25 cm • Fungemia: 10-30% of non-HIV patients
Treatment (Meningoencephalitis) • Induction therapy (2 weeks): • Amphotericin B (0.7-1 mg/kg/d) OR Ambisome (4-5 mg/kg/d) • Flucytosine (25mg/kg q6hr) • Consolidation therapy (8 weeks): • Fluconazole 400mg/d • Maintenance therapy (4-12 months): • Fluconazole 200mg/d
Idiopathic CD4 Lymphocytopenia (ICL) • Heterogeneous syndrome • Recognized in 1992 • CD4+ <300/L or <20% of total T cells on more than one occasion • Absence of any defined immunodeficiency or therapy associated with decreased levels of CD4+ T cells
Idiopathic CD4 Lymphocytopenia (ICL) • Although some develop opportunistic infections like those seen in HIV-infected patients, this syndrome is not like HIV • <1/2 with HIV risk factors • Wide geographic and age distributions • 1/3 are female (versus 16% for HIV) • Many remain clinically stable and do not progressively deteriorate • Reports of spontaneous reversal of the lymphocytopenia
Idiopathic CD4 Lymphocytopenia (ICL) • Immunological abnormalities tend to differ compared to HIV • ICL: CD8+ T cells, B cells, normal or Ig levels, no evidence of HIV-1, HIV-2, HTLV-1, HTLV-2, or any other mononuclear cell-tropic virus • No clustering of cases • Close contacts studied were HIV negative • Should be placed on OI prophylaxis depending on CD4 counts
References • Duncan, et al. Idiopathic CD4+ T-Lymphocytopenia -- Four Patients with Opportunistic Infections and No Evidence of HIV Infection. NEJM. Volume 328:393-398. • Kasper, et al. Harrison’s Principles of Internal Medicine, 16th edition. McGraw-Hill, New York. Volume I:1123,1183-1185.