Transcript CPC - Hopkins Medicine

CPC:38 year-old AIDS patient
with brain and pulmonary lesions
Gregory M. Lucas, MD PhD
Division of Infectious Diseases
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
Initial approach to an AIDS patient
with brain lesions
No mass effect, no
enhancement with IV
contrast
Mass effect, enhancement
with IV contrast
• HIV encephalopathy
• Progressive multifocal
leukoencephalopathy (PML)
• Abscess
• Malignancy
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
Toxoplasma gondii
• Cats are definitive host, many other animals
incidental host
• Seroprevalence in Baltimore ~10%
• Disease in AIDS is reactivation of latent infection
Pro
• Most common cause of brain lesions
in AIDS patients
• Multiple ring-enhancing lesions
typical (basal ganglia,
corticomedullary junction cerebrum
and cerebellum)
Con
• Toxo IgG negative
• Lung lesions atypical
CNS toxoplasmosis
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
Pro
• May produce nodular lung infiltrates
Con
• CRAG negative
• Brain abscesses rare with Histo
Pyogenic brain abscess
• Classification
– Extension from sinuses or ear,
– “Metastatic” – typically multiple
– trauma or post-operative
• S. aureus, Streptococci, anaerobic organisms
Pro
• Could pulmonary lesions be septic
emboli?
Con
• High-grade bacteremia should have
been readily detected
• No association with AIDS
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
Pro
• Appealing explanation for lung-brain
involvement
• ETOH and drug dependence
increases likelihood of exposure
Con
• AFB smears (induced sputum)
negative at outside hospital
• No meningitis
Tuberculomas
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)
Pro
• Lung-brain involvement common
• Pulmonary nodular infiltrates
common
Con
• No cavities or pleural effusion
Acid fast stain of N. asteroides
Nocardia pulmonary infection in
transplant patient
Nocardia brain abscess
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
Pro
• Dissemination to brain can occur
Con
• Rare
• No horse exposure
• Pulmonary infiltrates with R. equi
typically upper lobe cavities
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
Pro
Con
• Lung involvement with dissemination
to brain a hallmark of filamentous
fungi
• “Wedge” shaped pulmonary
infiltrates characteristic
• ?PE
• Rare complication in AIDS
• WBC 11,380 at presentation making
neutropenia unlikely
Aspergillus invading blood vessel
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
Pro
Con
• CNS lesions in NC – typically round,
fluid filled or calcified
• Not AIDS associated
• Wouldn’t explain pulmonary process
Neurocysticercosis
Malignancies
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)
Pro
• Most common cause of enhancing
brain lesion in AIDS patients with
negative toxo IgG
• Advanced immunosuppression
typical
Con
• Lung infiltrates would have to be a
second process
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
Pro
• PE related to hypercoagulability of
malignancy
Con
• Most common cancers metastasizing
to brain not particularly associated
with AIDS
• Pulmonary lesions don’t look like
metastases
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
Clinical diagnosis
• Pulmonary aspergillosis disseminated to
brain
• Nocardiosis
• Histoplasmosis
• Tuberculosis