3. Cryptococcosis in the Non-HIV Patient Kristen Amann, MD Morning Report August 12, 2009

4. 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 Non-HIV associated: 50%: glucocorticoids, immunosuppression Remainder: transplant, lymphoma, sarcoidosis, idiopathic CD 4 lymphocytopenia

5. 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

6. 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

7. 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

8. 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

9. Idiopathic CD 4 Lymphocytopenia (ICL) Heterogeneous syndrome Recognized in 1992 CD 4 + <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 CD 4 + T cells

10. Idiopathic CD 4 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

11. Idiopathic CD 4 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 CD 4 counts

12. Thanks!

13. 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, 16 th edition. McGraw-Hill, New York. Volume I:1123,1183-1185.