Alaka Ray, HMS Year III
Gillian Lieberman, MD
January 2005
Two Common Infections in
Two Uncommon Hosts
Alaka Ray, Harvard Medical School Year III
Gillian Lieberman, MD
Alaka Ray, HMS Year III
Gillian Lieberman, MD
Patient 1: Mr. G
Mr. G is a 38yo man, previously healthy,
presenting with
- 6 weeks of anorexia
- 30lb weight loss
- Increasing shortness of breath over one week
- Dyspnea on exertion
- Nonproductive cough over one week
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Alaka Ray, HMS Year III
Gillian Lieberman, MD
Patient 1’s Chest Radiograph
PACS, BIDMC
“Multifocal Ill-defined Opacities”
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Alaka Ray, HMS Year III
Gillian Lieberman, MD
DDx for Multifocal Ill-defined Opacities
ARDS, aspiration pneumonia, bronchopneumonia,
eosinophilic pneumonia, fungus disease, metastatic disease,
pneumoconiosis, PCP, pulmonary edema, PE with
infarction, sarcoid, TB, viral/mycoplasma pneumonia….
Diffuse opacity is a very common and nonspecific
finding, and must be correlated with clinical data.
4
Alaka Ray, HMS Year III
Gillian Lieberman, MD
More Information…
Patient 1 was tested on admission, and found to
be HIV positive, with a CD4 count of 26
cells/mm3.
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Alaka Ray, HMS Year III
Gillian Lieberman, MD
Correlation of CD4 Counts with Opportunistic
Organisms and Radiographic Findings
CD4 count
Radiographic findings, infections
>200cells/mm3
Bacterial pneumonia, TB (cavitary or non-cavitary
consolidation)
<200cells/mm3
Pneumocystis carinii pneumonia (reticular interstitial
pattern) MOST common pulmonary infection below
200 cells/mm3
50-200cells/mm3
Additional
Disseminated fungal infections and Kaposi’s
infections to keep
sarcoma
in mind below 200
<50cells/mm3AIDS-related lymphoma, MAI, CMV
cells/mm3
(nodular or reticular patterns)
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Alaka Ray, HMS Year III
Gillian Lieberman, MD
Patient 1’s FIRST Chest CT
Diffuse “Ground
Glass Opacity”
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PACS, BIDMC
Alaka Ray, HMS Year III
Gillian Lieberman, MD
DDX of “Ground Glass Opacity”
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Ground glass opacity is a CT finding consisting of an
area of increased attenuation with preservation of the
bronchial and vascular lung markings.
It is a common, but nonspecific, finding, occurring most
commonly in acute pneumonia, pulmonary hemorrhage,
pulmonary edema, interstitial diseases.
AIDS  PCP
Lung transplant  CMV
Recent BMT  Infection and diffuse alveolar
hemorrhage
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Alaka Ray, HMS Year III
Gillian Lieberman, MD
Our Patient Has…
Pneumocystis carinii Pneumonia
Classic symptoms are:
-low-grade fever
-non-productive cough
-progressive dyspnea
Godwin T. Structure and Function of the Lung.
http://edcenter.med.cornell.edu/CUMC_PathNotes/Respiratory/
Respiratory.html
The causative organism is unicellular, originally
classified as a protozoan, but recently recategorized
as a fungus. The strain that infects human lung
tissue is now known as P.jirovecii.
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Alaka Ray, HMS Year III
Gillian Lieberman, MD
Pneumocystis Pneumonia

This is an AIDS-defining illness. The first five
documented cases of AIDS in 1981 were cases of
PCP in Los Angeles.

Nearly 70% of all AIDS patients are infected with
this organism at least once. It almost always
strikes at CD4 levels below 200 cells/mm3. PCP
also infects patients with cancer, organ transplant
or those receiving immunosuppressive drugs.
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Alaka Ray, HMS Year III
Gillian Lieberman, MD
Lab Diagnosis and Treatment
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PCP is diagnosed by microscopic examination of
bronchoalveolar fluid or induced sputum, as it does not
grown in culture.
Treatment most commonly consists of Trimethoprimsulfamethoxazole, despite an emerging resistance.
HIV+ patients with CD4 counts below 200, as well as
other immunocompromised patients should receive
prophylaxis.
Other drugs used to treat PCP include Dapsone,
Atovaquone and Pentamidine.
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Alaka Ray, HMS Year III
Gillian Lieberman, MD
Findings in PCP
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Chest Radiograph: Up to 39% are normal.
Bilateral perihilar or diffuse infiltrates are
classically seen.
CT: Most commonly, patchy or diffuse ground
glass opacities are seen, along with occasional
septal thickening in more chronic cases.
In PCP, the ground glass opacity is thought to
represent fine alveolar exudate.
HRCT is believed to be >90% accurate in
diagnosis.
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Alaka Ray, HMS Year III
Gillian Lieberman, MD
Rare Findings
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Rare presentations: focal lobar consolidation,
lung nodules, bronchiectasis, mediastinal
adenopathy, pleural effusion.
Adenopathy and effusions are almost never seen,
and should trigger further investigation for a
different organism.
A cystic form of PCP is becoming increasingly
common over the last decade.
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Alaka Ray, HMS Year III
Gillian Lieberman, MD
Cystic Changes in PCP
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In its cystic form, PCP manifests as thin-walled,
irregularly-shaped air cysts in the peripheral
lung.
The cysts prefer the upper lung lobes – some
believe this to be due to aerosolized pentamidine
therapy in the 1990’s.
After infection resolves, cysts may persist or
shrink in size. Permanent interstitial fibrosis is
often seen as a long-term change.
14
Alaka Ray, HMS Year III
Gillian Lieberman, MD
Patient 1’s Worsening Chest Radiograph
PACS, BIDMC
Large cyst in Right middle lobe
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Alaka Ray, HMS Year III
Gillian Lieberman, MD
Back To Patient 1’s FIRST Chest CT

PCP changes are seen earlier (and better) on CT, than CXR!
Cystic
changes
ALREADY
visible
in the
anterior right
middle lobe
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PACS, BIDMC
Alaka Ray, HMS Year III
Gillian Lieberman, MD
Risk of Spontaneous Pneumothorax
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35% of patients with these subpleural air cysts
will manifest a spontaneous pneumothorax.
A patient with cystic changes on radiograph or
CT may thus present with acute onset dyspnea
and pleuritic chest pain.
Refractory air leaks in these patients may require
surgical intervention. This form of PCP has a
poor prognosis.
17
Alaka Ray, HMS Year III
Gillian Lieberman, MD
Later CXR and CT of Patient 1, with a Pneumothorax
from PCP-related Cystic Changes
PACS, BIDMC
18
Alaka Ray, HMS Year III
Gillian Lieberman, MD
Lessons from Patient 1…
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Radiologic findings are too nonspecific, unless
correlated with clinical information, such as a
CD4 count.
CT is vastly more sensitive than plain film in
detecting PCP.
The most common patterns seen in PCP are:
– Diffuse, bilateral infiltrates on plain film
– Ground glass opacity on CT
– Peripheral thin-walled cysts on CT and plain
film  watch out for pneumothorax!
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Alaka Ray, HMS Year III
Gillian Lieberman, MD
Patient 2: Mr. D
62 year old man diagnosed with CLL four years
previously, treated with various chemotherapy
regimens, including steroid therapy.
Now presenting with:
- increasing dyspnea on exertion
- nonproductive cough
- decreasing oral intake
- increasing fatigue
20
Alaka Ray, HMS Year III
Gillian Lieberman, MD
Patient 2’s Chest X-Ray
Paratracheal
prominence,
possibly due to
adenopathy
PACS, BIDMC
21
Alaka Ray, HMS Year III
Gillian Lieberman, MD
Patient 2’s Chest CT
Irregular opacity
surrounded by
“halo” of ground
glass opacity
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PACS, BIDMC
Alaka Ray, HMS Year III
Gillian Lieberman, MD
The CT “Halo Sign”
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The CT “Halo Sign” occurs when a dense nodule or
focal area of consolidation is surrounded by a “halo” of
ground glass opacity.
This can be caused by hemorrhagic pulmonary nodules
in diseases such as Wegener's Granulomatosis, metastatic
angiosarcoma, Kaposi’s sarcoma.
This sign may indicate angioinvasive pulmonary
aspergillosis, especially in patients with acute leukemia.
The necrotic nodule is surrounded by a hemorrhagic
halo. Later, these may become cavitating lesions.
(Collins 2001)
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Alaka Ray, HMS Year III
Gillian Lieberman, MD
Our Patient Has…
Aspergillosis
This is the most common
fungal pneumonia in
neutropenic cancer patients.
Nearly 20% of Bone Marrow
Transplant patients are also
affected.
Although it can occur in AIDS
patients, it is less common.
Mortality is known to be 6090%.
Unfortunately, our patient
succumbed to his disease.
Godwin T. Structure and Function of the Lung.
http://edcenter.med.cornell.edu/CUMC_PathNotes/Respiratory/
Respiratory.html
Therapy consists of a
prolonged course of
Amphotericin B.
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Alaka Ray, HMS Year III
Gillian Lieberman, MD
Types of Aspergillosis
The clinical and radiologic manifestations are
dependent on the category of pulmonary
manifestation:
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Local/Noninvasive
Semi-invasive
Angioinvasive
Airway-invasive
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Alaka Ray, HMS Year III
Gillian Lieberman, MD
Findings in Local/Noninvasive Aspergillosis
 A mycetoma or “fungus ball” is
formed within a pre-existing
cavity in the lung tissue.
 It may cause hemoptysis.
 Characteristically, an “air
crescent sign”is seen,
corresponding to the sliver of air
between the mycetoma and the
lung tissue.
Aspergilloma
Godwin T. Structure and Function of the Lung.
http://edcenter.med.cornell.edu/CUMC_PathNotes/Re
spiratory/Respiratory.html
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Alaka Ray, HMS Year III
Gillian Lieberman, MD
The Air Crescent Sign
This sign is
seen when a
mass grows
within a cavity
in the lung, or
when an
infected area
of the lung
necrotizes and
cavitates.
Air Crescent
between
mycetoma and
cavity wall
Ulusakarya A. Aspergilloma. N Engl J Med 2002; 346:256
In Angioinvasive Aspergillosis, the air crescent sign indicates immune
response to the infection.
Other rare causes: hydatid disease, hematoma, lung abscess, necrotic
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neoplasm
Alaka Ray, HMS Year III
Gillian Lieberman, MD
Findings in Semi-Invasive Aspergillosis
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Also known as chronic necrotizing aspergillosis
Associated with diabetes, alcoholism,
malnutrion, steroid therapy and advanced age
CT shows segmental consolidation in one or
both lungs. Multiple nodular opacities may also
be seen.
Findings often mimic reactivation tuberculosis
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Alaka Ray, HMS Year III
Gillian Lieberman, MD
Findings in Angioinvasive Aspergillosis
Godwin T. Structure and Function of the Lung. http://edcenter.med.cornell.edu/CUMC_PathNotes/Respiratory/Respiratory.html
Fungal Hyphae Invade and Occlude Pulmonary Arteries
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Alaka Ray, HMS Year III
Gillian Lieberman, MD
Findings in Angioinvasive Aspergillosis
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More common in severely neutropenic patients,
like our patient, Mr. D.
Hemorrhagic nodules lead to the CT “Halo
Sign”. Wedge-shaped areas of necrosis may be
seen.
“The Air Crescent Sign” is often seen, as
necrotic pulmonary tissue separates from the
surrounding tissues leaving partially air-filled
cavity. This usually indicates the return of
immune function.
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Alaka Ray, HMS Year III
Gillian Lieberman, MD
Findings in Airway-Invasive Aspergillosis
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Also known as aspergillus bronchopneumonia
Most common in neutropenic cancer and AIDS
patients
CT findings are consistent with peribronchial
disease. On HRCT, branching, nodular opacities
create the “Tree in Bud Sign” due to the filling
of airways with purulent material, thus making
them higher attenuation.
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Alaka Ray, HMS Year III
Gillian Lieberman, MD
The Tree-In-Bud Sign
Eisenhuber E. The Tree-In-Bud Sign. Radiology 2002; 222: 771-772
A spring tree in bloom
Centrilobular opacities connected
to branching lines
(Do you see the similarity?)
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Alaka Ray, HMS Year III
Gillian Lieberman, MD
Lessons from Patient 2…
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The most common fungal infection in neutropenic cancer
patients is Aspergillosis.
There are four manifestations of pulmonary aspergillosis:
local, semi-invasive, angioinvasive, and airway invasive.
The CT “Halo” sign is most indicative of angioinvasive
aspergillosis.
The “Air Crescent” sign may indicate either local
aspergilloma or resolving angioinvasive infection.
The “Tree in Bud” sign is seen in airway invasive
aspergillosis.
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Alaka Ray, HMS Year III
Gillian Lieberman, MD
References
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Aronchick JM. Pulmonary Infections in Cancer and Bone Marrow
Transplant Patient. Semin Roentgenol 2000; 35: 140-151
Collins J. CT Signs and Patterns of Lung Disease. Radiol Clin North Am
2001; 39:1115-35
Eisenhuber E. The Tree-In-Bud Sign. Radiology 2002; 222: 771-772
Franquet T, Gimenez A, Hidalgo A. Imaging of Opportunistic Fungal
Infections in Immunocompromised Patient. EJR 2004; 51:130-38
Godwin T. Structure and Function of the Lung.
http://edcenter.med.cornell.edu/CUMC_PathNotes/Respiratory/Respiratory.
html
Gottlieb MS. AIDS – Past and Future. N Engl J Med 2001; 344:1788-1790
Hiorns MP, Screaton NJ, Muller NL. Acute Lung Disease in the
Immunocompromised Host. Radiol Clin North Am 2001; 39: 1137-51
Maki D. Pulmonary Infections in HIV/AIDS. Semin Roentgenol 2000; 35:
124-139
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Alaka Ray, HMS Year III
Gillian Lieberman, MD
References
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Shah RM, Kaji AV, Ostrum BJ, Friedman AC. Interpretation of Chest
Radiographs in AIDS Patients: Usefulness of CD4 Lymphocyte Counts.
RadioGraphics 1997;17:47-58
Thomas CF, Limper AH. Pneumocystis Pneumonia. N Engl J Med
2004;350:2487-98
Ulusakarya A. Aspergilloma. N Engl J Med 2002; 346:256
35
Alaka Ray, HMS Year III
Gillian Lieberman, MD
Acknowledgments
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Dr. Karen Lee, Dr. Eamon Kato and Dr. Nishino, for
their invaluable help.
Dr. Gillian Lieberman, our course director
Pamela Lepkowski, our course administrator
Larry Barbaras, our webmaster
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