CPC:38 year-old AIDS patient with brain and pulmonary lesions

1. CPC:38 year-old AIDS patient with brain and pulmonary lesions Gregory M. Lucas, MD PhD Division of Infectious Diseases

2. Pre-Hopkins course CD4 cell count 3/mm3, HIV RNA>750,000 c/mL, OI � candidal esophagitis Crack cocaine and alcohol use, no ART, no OI prophylactic medications Admitted to outside hospital with subacute deterioration in mental status and seizure CNS and pulmonary lesions noted � induced sputum negative for PCP, AFB Rx with phenytoin, corticosteroids and fluconazole Discharged to hospice

3. Hopkins course P.E. � low-grade fever, hypoxia, encephalopathic, LUE flaccid Labs � Toxoplasma IgG, serum CRAG negative. CSF � mildly elevated protein, CRAG negative Brain imaging � innumerable enhancing masses with edema and mass effect Chest imaging � Nodular infiltrates (wedge-shaped), pulmonary embolism RLL

4. Could a viral CNS infection present this way? Herpes viruses � CMV, VZV, HSV can affect the CNS Typical picture is encephalitis often with ventriculitis CSF usually abnormal CNS mass lesions not seen Couldn�t explain pulmonary findings

5. Initial approach to an AIDS patient with brain lesions No mass effect, no enhancement with IV contrast HIV encephalopathy Progressive multifocal leukoencephalopathy (PML) Mass effect, enhancement with IV contrast Abscess Malignancy

6. Differential diagnosis of contrast-enhancing CNS lesions in an AIDS patient Abscess Toxoplasmosis Cryptococcosis, dimorphic fungi (histoplasmosis, coccidioidomycosis) Pyogenic abscess (Staph, Strep, polymicrobial) Tuberculosis Nocardiosis Filamentous fungi Neurocysticercosis Malignancy Primary CNS lymphoma Non-CNS cancer metastatic to brain

7. Toxoplasma gondii Cats are definitive host, many other animals incidental host Seroprevalence in Baltimore ~10% Disease in AIDS is reactivation of latent infection

8. CNS toxoplasmosis

9. Yeast: H. capsulatum (C. neoformans) Found worldwide, but geographical variation in intensity of exposure Lung � fungemia � CNS involvement in 10-20% (usually meningitis) Histoplasma antigen testing from serum or urine highly accurate in disseminated disease

12. Pyogenic brain abscess Classification Extension from sinuses or ear, �Metastatic� � typically multiple trauma or post-operative S. aureus, Streptococci, anaerobic organisms

13. Mycobacterium tuberculosis Infects 1/3 of global population Transition from latent to active disease occurs in 10% of HIV co-infected patients per year CNS involvement Meningitis � prominent basilar meningeal enhancement Tuberculomas � often multiple, solid-appearing grossly, often accompanied by meningitis Tuberculous abscess � quite rare, large, solitary, multiloculated

14. Tuberculomas

15. Nocardiosis �Higher-order� bacteria, gram-positive branching filaments, usually acid-fast Ubiquitous environmental saprophytes Defects in cell-mediated immunity important risk factor Manifestations Cutaneous infections (nodular lymphangitis, mycetoma) Pulmonary � disseminated (usually N. asteroides)

16. Acid fast stain of N. asteroides

17. Nocardia pulmonary infection in transplant patient

18. Nocardia brain abscess

19. Rhodococcus equi Gram-positive, weakly acid-fast rod May be mistaken for a �diptheroid� contaminant Causes pneumonia in foals Present in soil, 1/3 infected have exposure to horses In immunocompromised humans it presents as a TB mimic � indolent, upper-lobe, cavitary Difficult to treat

20. Filamentous fungi: Aspergillus, Pseudallescheria, zygomycosis Neutrophil defects strongest risk factor for invasive aspergillosis�bone marrow transplant, chronic granulomatous disease (CGD) Other risk factors � steroids, alcoholism Lung or sinuses typical portal of entry Dissemination to brain common, never meningitis Unusual in AIDS patients � very advanced disease, relative neutropenia, steroid use Notable aspect of pathogenesis is angioinvasion

21. Aspergillus invading blood vessel

22. Neurocysticercosis Taenia solium (pork tapeworm) Eat pigs (undercooked) � tapeworm infection � secrete eggs Eat poop (containing eggs) � cysticercosis (tissue infection with parasites) Infection common south of the Mexican border Accounts for 50% of adult onset seizures

23. Neurocysticercosis

24. Malignancies

25. Primary CNS lymphoma 2nd Most common cause of ring-enhancing brain lesions in AIDS patients in US Unlike peripheral lymphomas � PCNSL seen exclusively in advanced disease Solitary lesion in 50%, multicentric in 50% Non-Bx methods to distinguish from toxo: Toxo IgG, EBV PCR from CSF, metabolic function scans (SPECT, PET)

26. Malignancy metastatic to brain Most common tumors metastasizing to brain � lung, kidney, colon, breast, melanoma Kaposi�s sarcoma metastasis to brain extremely rare Peripheral lymphomas may metastasize to brain

27. Differential diagnosis of contrast-enhancing CNS lesions in an AIDS patient Abscess Toxoplasmosis Cryptococcosis Histoplasmosis Pyogenic abscess (Staph, Strep, polymicrobial) Tuberculosis Nocardiosis Aspergillosis Neurocysticercosis Malignancy Primary CNS lymphoma Non-CNS cancer metastatic to brain

28. Clinical diagnosis Pulmonary aspergillosis disseminated to brain Nocardiosis Histoplasmosis Tuberculosis