188.
ASPERGILLOSIS
Etiologic Agents: Aspergillus fumigatus ,
others: A. flavus, A. niger, A.nidulans, A.
terreus
Aspergillus – mold with septate branching
hyphae (2-4 um in diameter), identified by its
gross and microscopic appearance in culture.
PATHOGENESIS AND PATHOLOGY:
- ubiquitous in the environment, growing on
dead leaves, stored grain, compost piles,
hay and other decaying vegetation.
- Fungus can be isolated from potable water.
- Inhalation of spores is common
- Invasion of lung tissue is confined almost
entirely to immunocomrpmised px (90% of
whom 2 of the ff. 3 conditions are
operative:
a) granulocyte count in peripheral blood
of <500/uL
b) tx with supraphysiologic doses of
adrenal glucocorticoids
c) history of tx with other
immunosuppressive drugs such as
cyclosporine.
1.Invasive Aspergillosis – an occasional
complication of AIDS.
2.Aspergillosis infn in neutropenic px
-Hyphal invasion of blood vessels, thrombosis,
necrosis and hemorrhagic infarction.
3.Invasive Pulmonary aspergillosis
- from a chronic granulomatous disease of
childhood.
4. Pneumonitis – acute, diffuse and self-limited
- massive inhalation of spores by healthy persons
- epitheloid granulomas with giant cells and
central pyogenic areas containing hyphae
- px shd be tested for underlying chronic
granulomatous disease
5. Aspergilloma (balls of hyphe within cysts or
cavities), usually in the upper lobe may reach
several cm in diameter and may be visible on
CXR.
CLINICAL MANIFESTATIONS:
1. Allergic bronchopulmonary
aspergillosis
- in px with pre-existing asthma
(glucocorticoid dependent asthma) or
cystic fibrosis.
- Causes intermittent episodes of
wheezing, pulmonary infiltrates from
transient bronchial plugging, sputum
and blood eosinophilia, low grade fever
, and brownish or greenish flecks in the
sputum.
- Flecks: contain Aspergillus hyphae,
thick mucus, eosinophils and Charcoat
Leyden crystals.
- Some px with repeated exacerbations
develop central bronchiectasis and
progressive loss of pulmonary function.
2. Endobronchial Sparophytic Pulmonary
Aspergillosis
- Chronic productive cough,often with
hemoptysis, in a px with prior chronic lung
disease, such as TB, Sarcoidosis, Bronchiectasis
and Histoplasmosis.
3. Necrotizing Aspergillus Pneumonia.
- Aspergillus may spread from its endocavitary
or endobronchial site to the pleura.
- px have had saprophytic endobronchial
colonization, with or w/o superimposed
bacterial infxns.
4. Invasive Aspergillosis in the
Immunocompromised hosts
- acute, rapidly progressive, densely
consolidated pulmonary infiltrate.
- most common in px with acute leukemia and
recipients of tissue transplants.
- infxn progresses  direct extension across
tissue planes and hema dissemination to the
lung, brain and other organs.
Prognosis: very poor
-CT – one or more small pulmonary nodules.
As nodule enlarges, the dense central core of
infracted tissue becomes surrounded by edema
or hemorrhage, forming a hazy rim called
“HALO SIGN” (disappears in few daysas the
dense core enlarges)
When bone marrow fxn recovers, the infracted
central core cavitates, creating the “CRESCENT
SIGN”
4. Aspergillus sinusitis
3 forms:
a) a chronically obstructed paranasal sinus forms
a ball of hyphae , without tissue invasion.
b) a chronic fibrosing granulomatous
inflammation assoc with Aspergillus hyphae
within tissue may begin in the sinus  spread
slowly to the orbit and the brain.
healthy , presenting with painless proptosis,
nasal obstruction or dull aching pain.
c) Allergic fungal sinusitis – (more common
cause:Curvularia, Alternaria)
- Px with a history of chronic allergic rhinitis,
sometimes with nasal polyps, but are otherwise
9. Aspergillus may infect intracardiac or
intravascular prosthesis.

CT or MRI – soild soft tissue mass pushing out DIAGNOSIS:

the lateral wall of the ethmoid sinus or the
medial wall of the maxillary sinus.
Sinus exploration : mucosa is thickened and
inflamed but intact. Within the cavity, sticky
mucopus with strands of neutrophils, eos and
Charcoat Leyden crystals, and occasional hyphae
are found.
5. ASPERGILLOSIS IN HIV INFECTED PX
- most commonly involves the LUNG (well
localized, white necrotic pseudomembranes full
of hyphae or ulcers may dev in the trachea or
major bronchi)
- fever, cough and dyspnea
- CD4+ cell count is <50/uL (allergic form even if
>50/uL)
- half of px: neutropenic or have been treated
with Glucocorticoids
RADIO: bilateral diffuse or focal pulmonary
infiltrates with a tendency to cavitate
-progression of bronchitis  pneumonia
6. OTOMYCOSIS
- the growth of Aspergillus on cerumen and
detritus within the external auditory canal
7. ASPERGILLUS KERATITIS
- Trauma to the cornea
8. ASPERGILLUS ENDOPHTHALMITIS
-Introduction of Aspergillus into the globe by
trauma or surgery
1. Endcobronchial colonization or infection
-Repeated isolation of Aspergillus from sputum
or the demonstration of hyphae in sputum or
bronchoalveolar lavage fluid
2. Invasive Aspergillosis
- even with a single isolation of Aspergillus from
the sputum of a neutropenic px or a
hematopoietic stem cell transplant recipient
with pneumonia, particularly a child or a non
smoker.
3. Patients with advanced AIDS, fever and cough
- isolation of Aspergillus from respiratory
secretions , prompt bronchocopy
- Fungus ball of the lungs – CXR
- IgG Antibody to Aspergillus antigens in the
serum of colonized px and in px with fungus
ball.
(serum IgG conc: > 1000 ng/mL)
4. Biopsy for the dx of Aspergillosis of the lung
mose and paranasal sinus, bronchi, or sites of
dissemination.
5. Blood cultures are rarely positive, even in px
with infected heart valves (native or prosthetic)
- detection of galactomannan antigen in serum
suggest the dx
6. Histology – Aspergillus hyphae
7. Culture – distinguish aspergillosis from
pseudallescheriasis

TREATMENT:
Table 188-1 page 1189
TYPE OF DISEASE
Fungus ball of the lungs
Allergic bronchopulmonary
aspergillosis
Invasive aspergillosis
PREFFERED TREATMENT
Surgical resection (lobectomy if
with severe hemoptysis)
Short courses of Glucocorticoids
(200mg twice daily)
Voriconazole (6mg/kg twice
daily for 2 doses; for later oral
admi, 200mg twice daily),
liposomal (5mg/kg daily)or
conventional Amphotericin B
(1-1.5mg/kg daily)
ALTERNATIVES
Bead embolization for hemoptysis
Itraconazole prophylaxis (to treat
exacerbations)
Amphotericin B colloidal dispersion
(6mg/kg daily) or lipid complex (5mg/kg
daily), IV Itraconazole (200 mg twice
daily for 4 doses, then 200 mg daily) or
IV Caspofungin ( 70 mg once, then 50
mg daily)

Addtnal notes:
-Amphotericin B colloidal dispersion – shows equivalent efficacy with Conventional Amphotericin B, it is less
nephrotoxic and more often causes infusion-related chills and fever.
-IV Itraconazole – contraindicated in px with CREA clearance of <30mL/min
-IV Capsufungin - for patients in whom therapy with other drug fails
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