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Pneumocystis Carinii

Pneumonia
Elizabeth Wozniak, MS4
Diagnostic Radiology
December 16, 2005

Background
First identified in the early 1900s by
researchers working with guinea pigs
and rats
Initially classified as a protozoan
based on morphologic appearance
Exists in two forms: trophozoites 1-4 m
and cysts 8 m in diameter

Reclassified in 1988 as a fungus based


on genomic analysis

Background
Pneumocystis species have been
identified in most mammals and are
species specific
Human form was recently renamed
P. jirovecii
There is still little known about
Pneumocystis because it cannot be
cultured

Epidemiology
Serologic studies
show universal
seropositive status by
age two
Route of transmission
is currently unknown
Likely airborne
transmission from
person to person
Possible environmental
transmission as well

Risk Factors
Impairment in Cellular Immunity
HIV:
CD4 count < 200

Chronic corticosteroid therapy


Prednisone 16 mg qd for longer than eight
weeks

Others including: transplant patients,


chemotherapy recipients, congenital
immune system defects, premature
infants, and malnutrition

Pathophysiology
Pneumocystis infection is specific to the
lung
Trophozoites bind tightly to alveolar
epithelium, but do not invade cells
CD4 T cells recognize pathogen and
recruit macrophages
Macrophages release TNF- which
propagates immune response through
further recruitment and cytokine release

Pathophysiology continued
Results in a large
inflammatory response
which can lead to
diffuse alveolar damage,
impaired gas exchange,
and respiratory failure
Respiratory involvement
and death is more
closely correlated with
degree of lung
inflammation than with
organism burden

HIV vs. non-HIV


HIV
High fungal load
Little inflammation
Spared oxygenation

Non-HIV
Low fungal load
Large inflammation
Poor oxygenation

Signs and Symptoms

Progressive dyspnea, DOE


Non-productive cough
Low grade fever
Hypoxemia
Tachypnea
Tachycardia
Often normal pulmonary exam vs. mild
crackles
Time course

HIV: gradual onset in 2-6 weeks


Non-HIV: abrupt onset in 4-10 days, can correlate
with taper or increased dose of corticosteroids

Diagnosis
Requires microscopic evidence of Pneumocystis

Sputum induction: diagnostic yield of 50-90% in HIV


Bronchoalveolar lavage: diagnostic yield of >90% in HIV
Rarely requires transbronchial or surgical lung biopsy
Diagnostic yield much lower in non-HIV cases (given low
fungal burden). Consider empiric treatment if negative
sputum/BAL but high suspicion

Histologic evidence
Trophozoites stain with modified Papanicolaou, Wright
Giemsa, or Gram-Weigert stains
Cysts stain with Gomori methenamine silver, cresyl echt
violet, toluidine blue O, or calcofluor white stains
Monoclonal antibodies bind both forms
PCR is not currently available but a future consideration

Diagnosis continued
Gomori methenamine silver (GMS)
stain from BAL specimen showing
crushed ping-pong ball
appearance of cyst wall

Diagnosis continued
Wright-Giemsa stain showing
trophozoites within foamy exudates
(at arrows) from BAL

Diagnosis continued
Calcofluor white stains the fungal
cyst wall for rapid diagnosis

Diagnosis continued
Immunofluorescence showing
trophozoites (arrowheads) and cysts
(arrows)

Radiographic Findings
Typically see bilateral, ground glass opacities
that progress over time to become homogenous
and diffuse
10% of HIV patients will show upper lobe cysts
Less common to see solitary or multiple nodules,
upper lobe predominance, or pneumothorax
Rare to see pleural effusion or lymphadenopathy
(search for another cause)
HRCT is more sensitive during early stages
when CXR will likely appear normal

PA Chest Radiograph
68 y/o on long
term corticosteroids.
Demonstrates
bilateral, perihilar,
R > L, ground glass
opacities

PA Chest Radiograph
Progressive
disease showing
extensive ground
glass opacification
with consolidation

PA Chest Radiograph
Diffuse ground
glass opacity with
reticular pattern
indicating cyst
formation

PA Chest Radiograph
Diffuse, ground
glass opacities with
large left sided
pneumothorax
Cysts predispose
patients to pneumothorax

PA Chest Radiograph
Patchy, ground
glass opacities in the
apices in an
AIDS patient on
pentamidine
prophylaxis

CT Chest
Patchy, bilateral
ground glass
opacities in a 9
month-old HIV
positive child

Radiographic Differential
Diagnosis
Non-cardiogenic edema
Diffuse pulmonary hemorrhage
Wegeners, Goodpastures, etc.

CMV pneumonitis
Hypersensitivity pneumonitis
Pulmonary alveolar proteinosis

Treatment
Trimethoprim-Sulfamethoxazole 15-20 and 75-100
mg/kg respectively given daily divided into BID
dosing
Some strains with emerging mutations in
dihydropteroate synthase gene, sulfa drug target
Not yet clinically significant

For sulfa allergy: primaquine + clindamycin,


atovaquone, or pentamidine
Corticosteroids decrease morbidity and mortality in
severe disease. Indicated if:
PaO2 < 70 mm Hg
P[A-a]O2 > 35 mm Hg

Prednisone 40 mg bid x five days with taper

Prognosis
Based on severity of inflammation
Which patients have a better prognosis?
HIV
10-20% mortality with primary infection.
Increased with mechanical ventilation

Non-HIV

30-60% depending on cause of immunosuppression

LDH level has been linked to prognosis

LDH represents degree of underlying inflammatory


damage to lung
Poorer outcomes when it is elevated at diagnosis
or continues to rise despite treatment

Prophylaxis
Primary prophylaxis

HIV patients with CD4 count < 200 or with a


history of oral candidiasis
Patients taking corticosteroids > 16 mg for > 8
weeks

Secondary prophylaxis

Lifelong after developing PCP infection

Medications:

TMP-SMX
Alternatives: dapsone, pentamidine, atovaquone

Can prophylaxis ever be discontinued?


Yes, if CD4 count > 200 for > 3 months

References
Thomas, C.F and Limper, A.H. Pneumocystis Pneumonia.
New England Journal of Medicine: 350;24. June 10, 2004.
Gosselin, M.V. Diffuse Lung Disease in the
Immunocompromised Non-HIV Patient. Seminars in
Roentgenology: 37;1. January, 2002.
Gosselin, M.V. Pneumocystis Carinii Pneumonia. Book
chapter.
Chamberlain, J.J. and Ries, K. Pneumocystis carinii.
Current Diagnosis and Treatment in Infectious Diseases,
2001.
PCP treatment guidelines in HIV at www.idsociety.org
Radiographic images obtained from UCSF Department of
Pathology website
Pathology images obtained from NEJM article

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