Download PowerPoint 프레젠테이션

Cryptococcal
pneumonia
Chest conference
2003. 6. 20.
한창훈
INTRODUCTION
 Pulmonary fungal infection:
Retrospective study, 140 patients, 1988-1997
Aspergillus(57%), Cryptococcus(21%), Candida(14%)
Chest 2001;120:177-84
 Immunocompetent - rare
in the Asia-Pacific region
Reported annual incidence of cryptococcosis: 5/million
Pulmonary cryptococcosis 30%
Respirology 2001;6:351-5
INTRODUCTION
 C. neoformans
encapsulated, yeast like organism
world wide distribution
present in the soil and in bird(particulary pigeon)
associated with exposure of bird droppings
usually manifested as meningitis
INTRODUCTION
 The lungs:
thought to be the initial site of almost all infections
usually through inhalation of small yeasts or
Basidiospores
-> deposition in the alveoli and terminal bronchioles
-> small focal pneumonitis
 The immune status:
the most important element in determining
the subsequent course of the infection
IMMUNOCOMPETENT HOSTS
Symptoms
some symptomatic
 large population: exposed to C. neoformans
subclinical primary infections:
asymptomatic - very common the vast majority
 one of reviews, in 1966, 101 patient
32% asymptomatic, incidental finding
Cough (54%), Chest pain (46%),
sputum production  (32%), Fever (26%),
Weight loss (26%), Hemoptysis (18%)
IMMUNOCOMPETENT HOSTS
Diagnosis
usually made by culturing the organism from
sputum or another specimen
 Chest radiography
the most common: well-defined, non-calcified
nodules, either solitary or a few
Rare: cavitation in cryptococcal nodules
Others: lobar infiltrates, hilar and mediastinal
adenopathy, and pleural effusions
IMMUNOCOMPETENT HOSTS
 Cultures
characteristically encapsulated yeast forms in
specimens of sputum, BAL or tissue
-> establish Dx
clinically silent cryptococcal nodules:
sampled to R/O the possibility of malignancy
pleural effusion: likely to be exudate,
yeast forms - sometimes, Cx - usually (+)
IMMUNOCOMPETENT HOSTS
 Cryptococcal antigen testing
screening test for pulmonary cryptococcosis:
less likely to be (+) in immunocompetent than
immunocompromised
(+) serum Ag titer: indicative of infection and
suggests extrapulmonary spread
testing pleural fluid:
can be a very useful in suspected cases in which
cultures (-)
Diagnosis
CT scans of 11 patients (7 immunocompromised,
4 immunocompetent) with proven pulmonary
cryptococcosis
Pulmonary nodules, either solitary or multiple,
were the most common CT finding, present in 10
of 11 patients (91%)
associated findings included masses (n = 4), CT
halo sign (n = 3), and consolidation (n = 2)
JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY
2002;26:330-334
IMMUNOCOMPETENT HOSTS
Management
Consideration for the presence of
extrapulmonary infection, especially CNS
assess whether there is some underlying
disorder present that may put the patient at
higher risk for disseminated disease
not require respiratory isolation: no cases of
spread from person to person via the
respiratory route
IMMUNOCOMPETENT HOSTS
 When to test for CNS involvement
Dissemination to CNS from lungs:
very rare, not recommend routine sampling of CSF
CSF for cryptococcal Ag testing and Cx:
neurologic Sx
underlying condition predisposes to dissemination
serum cryptococcal Ag titer is very high (>1:250),
IMMUNOCOMPETENT HOSTS
 Drainage or surgery
Pleural effusions Tx:
systemic therapy alone, rarely require drainage
Surgical excision of infected pulmonary tissue:
only indicated in cases of pseudotumor-like
masses that impinge on adjacent structures
IMMUNOCOMPETENT HOSTS
 Antifungal therapy
Symptomatic pulmonary infection:
fluconazole or amphotericin B
Fluconazole (400 mg per day):
preferred for most patients since PO
less toxic than amphotericin B
IMMUNOCOMPETENT HOSTS
 Antifungal therapy
Amphotericin B (0.7 mg/kg per day) plus
flucytosine (100 mg/kg per day):
preferred for induction therapy
with CNS involvement or
extensive, multi-organ disease
induction for the first 14 days
if improvement -> can be changed to fluconazole
Isolated symptomatic pulmonary dz:
3-6 months, depending on the extent of infection
IMMUNOCOMPETENT HOSTS
 Antifungal therapy
aSx with (-) serum Ag:
may not require any systemic therapy
aSx with detectable serum Ag:
very low likelihood of symptomatic systemic
dissemination < Tx with fluconazole is relatively
benign and likely to be curative
regardless of Sx with detectable serum Ag, (+) Cx:
consider therapy in all patients
IMMUNOCOMPETENT HOSTS
 Antifungal therapy
Guidelines from
the Infectious Diseases Society of America (IDSA)
on the treatment of pulmonary cryptococcosis
for mild-moderate pulmonary disease:
fluconazole (200-400 mg/d for 6-12 m),
itraconazole (200-400 mg/d for 6-12 m)
or amphotericin B
(0.5-1.0 mg/kg/d for a total of 1-2 g)
IMMUNOCOMPROMISED HOSTS
 probably due to reactivation of latent infection
reinfection with another strain or
primary infection are also possibilities
 more Sx than immunocompetent
more likely to present with extrapulmonary dz
IMMUNOCOMPROMISED HOSTS
 Risk factors for pulmonary cryptococcosis:
HIV infection
Malignancies
Stem cell and solid organ transplantation
Cirrhosis
Renal failure
Chronic lung disease
Diabetes
Cushing's syndrome
Sarcoidosis
Sickle cell disease
Treatment with corticosteroids
IMMUNOCOMPROMISED HOSTS
 Symptoms in HIV-negative patients
In 1981 review
28/34 extrapulmonary dz
All 28 with disseminated disease:
fever (63%), chest pain (44%), dyspnea (27%),
cough (17%), hemoptysis (7%)
Dissemination to the CNS 61%
All cases were diagnosed within 20 weeks
after the pulmonary presentation
IMMUNOCOMPROMISED HOSTS
 Symptoms in HIV-negative patients
In 2001 review of 109 patients
cough (61%), dyspnea (48%), fever (29%),
weight loss (19%), pleuritic chest pain (19%),
night sweats (16%)
Chest radiographs:
closely resemble immunocompetent patients
IMMUNOCOMPROMISED HOSTS
 Symptoms in HIV-infected patients
More acute and severe than in other groups
fever (81-94%), cough (63-71%), dyspnea (550%), headache (41%)
Some quite hypoxic, ARDS
Severity of Sx and extent of dissemination:
inversely proportional to CD4 lymphocyte count
most symptomatic cases with count <100
Dissemination from lungs to CNS: 65-94%
IMMUNOCOMPROMISED HOSTS
 Symptoms in HIV-infected patients
Chest radiographs:
interstitial infiltrates that can mimic PCP
alveolar infiltrates, LAP, mass lesions, and
small pleural effusions
IMMUNOCOMPROMISED HOSTS
 Diagnosis
respiratory specimens grow C. neoformans
in the setting of a compatible clinical syndrome
Bronchoscopy:
may be indicated in advanced HIV infection in
order to R/O other infections(PCP)
IMMUNOCOMPROMISED HOSTS
Cryptococcal antigen testing
(+) in virtually all with HIV infection
56-70% other underlying immunocompromising
conditions
excellent screening test
in immunocompromised
with atypical presentations of respiratory dz
IMMUNOCOMPROMISED HOSTS
 Treatment
all with pulmonary cryptococcosis
amphotericin B (0.7 mg/kg/d IV) plus
flucytosine (100 mg/kg/d PO in 4 divided)
Relapse: In 2001 review
immunocompromised, without HIV infection
2/122(1.6%) treated initially with
amphotericin B plus flucytosine
4/78 (5%) and 5/70 (7%) with fluconazole
alone and amphotericin B alone
IMMUNOCOMPROMISED HOSTS
 Duration of therapy
induction therapy with amphotericin B±flucytosine:
for 14-21 days depending on the response and the
extent of infection
-> change to fluconazole (400 mg/d PO)
Total duration of fluconazole for 6-12 months
HIV-infected: chronic suppressive therapy
with 200 mg/d of fluconazole
IMMUNOCOMPROMISED HOSTS
 Maintenance therapy
insufficient data
chronic suppressive therapy can be stopped
persistent increases in CD4 > 200
responded to therapy, subsequently must
undergo cancer CTx or intensive therapy for
graft rejection within 2 years of Dx:
should be covered with fluconazole during
these treatments to prevent recurrence