Pulmonary aspergillosis

[Guest guest]

Dearest Saline Support Group:

I'm going to be reposting some of the wonderful research that

beloved Kathi " Pureheart " Leahy posted over the years.

I know several women with saline and double lumen implants who were

diagnosed with aspergillosis.

With love from Ilena

www.BreastImplantAwareness.org

~~~~~~~~~~~~~~~~~~~~~~~~~~~~

Kathi Jun 17 2003, 3:03 pm

Newsgroups: alt.support.breast-implant

From: purehe...@... (Kathi)

Local: Tues, Jun 17 2003 3:03 pm

Subject: Pulmonary aspergillosis, part 1: allergic disease and

mycetomas; recognizing the pattern of illness is key

Pulmonary aspergillosis, part 1: allergic disease and mycetomas;

recognizing the pattern of illness is key.

Author/s: Sandhya Khurana, Kuntal Thaker, C. Kane

Issue: May, 2002

ABSTRACT: The diagnosis of allergic bronchopulmonary aspergillosis

(ABPA) usually is based on the presence of asthma, peripheral blood

eosinophilia, markedly elevated IgE levels, immediate skin test

reactivity to Aspergillus antigen, and precipitating antibodies to

Aspergillus species in the serum. Systemic corticosteroids, such as

prednisone, should be used to treat ABPA. The classic radiographic

appearance of a mycetoma, a cavitary lesion with an intracavitary

mass

formed by a collection of fungal hyphae, is readily identifiable if

an

aircrescent sign is seen. In patients with unilateral lesions and

good

lung function (forced vital capacity, more than 50% of predicted),

surgery is often the treatment of choice. Surgical resection for

patients with bilateral pulmonary parenchymal disease must be

considered on an individual basis. (J Respir Dis. 2002;23(5):300-

307)

**********

Aspergillosis represents an important group of pulmonary diseases

that

span the spectrum from asymptomatic colonization to IgE-mediated

hypersensitivity reactions or tissue invasion with dissemination and

death. Since aspergillosis is encountered frequently in the acute

care

setting, it is important that you recognize the clinical patterns of

disease and understand the principles of therapy

The spectrum of illness caused by Aspergillus is related to the

presence or absence of hypersensitivity structural lung disease, and

immune factors. Otherwise healthy persons do not generally encounter

problems with this organism if they are not allergic or

hypersensitive. Patients with bullae, cysts, or cavities are at risk

for mycetomas. Immunosuppressed persons can experience any of the

more

invasive types of illness.

This article will focus on the diagnosis and treatment of allergic

bronchopulmonary aspergillosis (ABPA) and mycetomas. In a coming

issue

of The Journal of Respiratory Diseases, Drs Khurana and Kane will

review chronic necrotizing (chronic invasive) pulmonary

aspergillosis,

acute invasive pulmonary aspergillosis, and pulmonary aspergillosis

in

HIV-infected patients.

Aspergillus

Since fungi of the Aspergillus genus are ubiquitous and grow on

decaying matter, exposure to their spores is inevitable. (1) The

organism, its fruiting body, and the spores that can be aerosolized

into the environment are shown in Figure 1. Although there are more

than 300 species of Aspergillus, only a few affect humans.

Aspergillus

fumigatus is the most common, followed by Aspergillus flavus. Rarely

encountered species include Aspergillus niger, Aspergillus clavatus,

and Aspergillus nidulans.

Although Micheli first recognized Aspergillus as an organism in

1729,

the first cases in humans were not noted until the mid19th century.

(2) Approximately 100 years later, invasive aspergillosis was first

described as an opportunistic infection. (3)

Currently, the range of aspergillosis is expanding, and the

incidence

of invasive disease seems to be rising, largely because of increased

use of immunosuppressive therapies and transplantation. Despite

repeated exposure to this group of organisms, disease as a result of

tissue invasion is relatively uncommon. Neutropenia and

corticosteroid

use are the most common risk factors. (45)

Allergic bronchopulmonary aspergillosis

In some persons, hypersensitivity to Aspergillus species can cause

asthma, hypersensitivity pneumonitis (HP) (extrinsic allergic

alveolitis), and ABPA. HP that is caused by Aspergillus is

indistinct

clinically from HP caused by other pathogens, except that the

inciting

antigen must be aerosolized from Aspergillus growing on decaying

organic matter. HP is also known as malt workers lung or farmers

lung,

although the more specific entities are caused by hypersensitivity

to

other pathogens, namely the thermophilic organisms. (6)

Allergic asthma associated with inhalation of Aspergillus is rare

and

is clinically distinct from ABPA. Patients with classic IgE-mediated

allergic asthma have serum IgE levels that range from 10 to 250

ug/L.

(7) Markedly elevated levels of IgE, usually exceeding 500 to 1000

ug/L, characterize ABPA. (6,8)

* Diagnosis: Although the diagnosis of ABPA does not require all of

the following clinical characteristics, the first 5 usually are

present: asthma, peripheral blood eosinophilia, markedly elevated

IgE

levels, immediate skin test reactivity to Aspergillus antigen,

precipitating antibodies to Aspergillus species in the serum,

pulmonary infiltrates that may be migrating, and central

bronchiectasis (Table). A series of radiographic findings obtained

from a patient who had ABPA with fleeting pulmonary infiltrates and

migratory lobar collapse (secondary to mucous plugging) are shown in

Figure 2. A follow-up thoracic CT scan of the same patient showed

bronchiectatic changes (Figure 3).

The clinical course of ABPA is characterized by recurrent acute

episodes with intervening remission (duration is difficult to

predict). During remission, underlying asthma often requires

treatment. Recurrent acute flares can lead to severe bronchiectasis

or

end-stage fibrosis. (6)

ABPA was first recognized as a common disease in the United Kingdom.

(9) Initially, in the United States, ABPA was thought to be quite

rare, (10) but now it is common in the Midwest, (11) with a lower

incidence in the mid-Atlantic region. ABPA associated with cystic

fibrosis is seen often in Great Britain (12) but is seen less in

North

America. (6)

* Treatment: Systemic corticosteroids should be used to treat ABPA.

Prednisone (0.5 mg/kg) for 2 to 6 weeks will effect radiographic

clearing of infiltrates in most patients. After this, prednisone can

be tapered to alternate-day dosing for several months. (8) The total

duration of therapy is based on symptoms, eosinophilia, and the

serum

IgE level. We recommend frequent checking of the IgE level during

the

first year of therapy, establishing a baseline to use for ongoing

monitoring. (13) The IgE level rarely returns to the normal range,

but

the new baseline level should be significantly lower than the

pretreatment level.

Asthma flares with a significant rise in the IgE level or new

infiltrates indicate an exacerbation of ABPA and the need to resume

oral corticosteroids. Inhaled corticosteroids are not effective in

the

acute flares of the illness but are helpful in treating underlying

asthma during remission. Some physicians suggest periodic plain

radiographic imaging for patients in remission, because infiltrates

can recur with minimal symptoms. (14)

Use of itraconazole has been controversial, although anecdotal

reports of response to treatment with rapid resolution of symptoms

and

a decline in serum IgE levels have suggested an adjunctive

therapeutic

role. (15,16) In 2000, s and colleagues (17) reported on a

double-blind, placebo-controlled trial of itraconazole in

corticosteroid-dependent patients with ABPA. At reputable centers,

55

patients were randomized to itraconazole, 200 mg twice daily, or

placebo. Patients receiving itraconazole had further reduction in

corticosteroid dose and greater improvement in lung function and

exercise tolerance than those receiving placebo. The drug was well

tolerated without significant toxicity.

Thus, itraconazole may have a potential role in

corticosteroid-dependent patients with ABPA. However, its use cannot

be recommended in all patients until further studies have been

reported. Currently, we believe itraconazole should be used in

patients with ABPA who require daily corticosteroid treatment for

more

than 3 months because of continuing symptoms.

Mycetomas

Usually, this form of Aspergillus infection is seen after the

occurrence of isolated hemoptysis without constitutional symptoms.

It

may be evident on routine radiologic imaging of patients with

various

chronic lung diseases, such as emphysema or sarcoidosis.

Generally, this form of aspergillosis occurs in preexisting cysts or

cavities, leading to the formation of mycetomas or fungus balls.

Rarely, mycetomas may remain as the residua of invasive parenchymal

aspergillosis after reversal of the immune defect and stabilization

with antifungal therapy.

* Diagnosis: The classic radiographic appearance is a cavitary

lesion

with an intracavitary mass of variable size (diameter, 1 to 20 cm)

formed by a collection of fungal hyphae. A fumigatus is the species

identified most often, but others (A flavus, A niger,

Pseudallescheria

boydii) may be encountered. Certain bacteria can mimic the

appearance

of a fungus ball, such as Actinomyces israelii (a filamentous

gram-positive rod that can cause the air-crescent sign) in pulmonary

actinomycosis. (18)

The worst complication of mycetomas is massive hemorrhage, which

usually occurs unexpectedly and often requires emergent management

decisions. Episodes may occur without warning and can be fatal. The

presence of fungus causes bleeding from the epithelialized lining of

the cavity wall without significant tissue invasion. The exact

mechanism remains controversial. Mycetomas also can become

suppurative

locally.

The cause of the underlying cavitary lung disease may be

inflammatory,

infectious, or neoplastic. Cavities resulting from pulmonary

tuberculosis were once common; however, the incidence of mycetomas

from tuberculosis has decreased over the last 50 years. Generally,

sarcoidosis leads to upper lobe fibrosis and subsequent cyst or

cavity

formation in the areas of destroyed lung. These areas are possible

sites for aspergilloma formation. (19) Other causes include

bronchial

cysts, bronchiectasis, emphysematous bullae, and neoplasm. (20)

Aspergilloma may occur in the setting of cystic fibrosis. (21) The

colonized cysts range in diameter, from 2 to 20 cm.

The characteristic radiologic appearance of a mycetoma makes it

identifiable readily, particularly if an air-crescent sign is seen

(Figure 4). Movement of the intracavitary mass with change in the

patient's position helps make the diagnosis.

However, mycetomas may be hidden in scarred or fibrotic lung, making

the diagnosis difficult on plain radiographic films and CT scans.

Aspergillomas may be unchanged for years, grow, or gradually

resolve.

Typically, the diagnosis of an aspergilloma is suggested by the

radiographic appearance; however, confirmation requires the culture

of

the organism from the lesion (needle or bronchoscopic biopsy) or

demonstration of precipitins that are invariably present when

testing

is done in reliable laboratories. Radiologic criteria alone are not

always sufficient because neoplasms or lung abscesses can produce

similar rounded masses surrounded by a halo. Examination of sputum

usually does not reveal the causative organism.

When the presenting symptom is hemoptysis, bronchoscopy frequently

is

recommended for localization of the bleeding site. Pursel and

Lindskog

(22) reported successful bronchoscopic localization of the source of

bleeding in 86% of patients with active bleeding. However, when

parenchymal disease occurs bilaterally and bleeding is profuse, this

may not be possible. Use caution in acutely bleeding patients with

diffuse or bilateral disease to avoid resection of the wrong lobe or

lesion. Decisions are easier in patients with isolated radiographic

lesions, although bronchoscopic localization generally is still

recommended. In our experience, some patients confidently can sense

the side with bleeding, but this alone cannot form the basis for

guiding surgery

* Treatment: Because hemorrhage is unpredictable, treatment of

mycetomas is difficult. At our institution, at least 7 known

fatalities have resulted from hemorrhage in patients with

sarcoidosis.

(19) The goal of therapy is to control acute, severe episodes of

hemorrhage and prevent recurrence in patients with known mycetomas.

In patients with unilateral lesions and good lung function (forced

vital capacity, more than 50% of predicted), surgery is often the

treatment of choice. Surgical resection for patients with bilateral

pulmonary parenchymal disease must be considered on an individual

basis. (19) Rates of hemorrhage may be as high as 74%, (20) with

massive hemoptysis (more than 600 mL/24 h) and fatality occurring in

10% to 28% of patients. (19,23) We are not aware of a predictive

model

using clinical criteria that can help identify patients at risk for

major bleeding.

Consider alternative measures for acute ongoing bleeding in patients

who are unfit for surgical resection. Unfortunately, therapeutic

options are based on limited studies consisting primarily of case

reports or small case series. Intravenous amphotericin B has no

therapeutic benefit for acute bleeding. There are anecdotal reports

of

improvement from intracavitary instillation of amphotericin B,

(24,25)

but this approach is not widely used.

A report of successful treatment of life-threatening bleeding in 11

cases by intracavitary instillation of iodides requires

corroboration.

(26) Lung cavities were flushed 3 times daily for 3 to 4 weeks via

the

percutaneous or transcricothyroid route. With the absence of a

control

group for comparison, it is difficult to draw conclusions from this

study.

Although itraconazole has been used in treating patients with

aspergilloma and recurrent bleeding, it has not been used in the

setting of acute bleeding. Limited case series and individual

reports

have demonstrated both clinical and radiographic response, but

relapse

can occur in patients when the drug is discontinued. (27-29)

Embolization to control active bleeding is difficult, but it has

proved effective in experienced hands. Long-term control and

prevention of rebleeding is not necessarily achieved with

embolization. (30,31)

Since no prospective trials have addressed the management issues

that

arise in patients with bleeding aspergilloma, there is little

consensus on management. The options--surgery, antifungal

chemotherapy, instillation of antifungal agents via catheter, or

observation--must be weighed on an individual basis, with

consideration of local available resources.

[Editor's note: In an upcoming issue of The Journal of Respiratory

Diseases, Drs Khurana and Kane will discuss chronic necrotizing

(chronic invasive) pulmonary aspergillosis, acute invasive pulmonary

aspergillosis, and pulmonary aspergillosis in HIV-infected

patients.]

Table

Diagnostic criteria for allergic bronchopulmonary aspergillosis *

Asthma

Peripheral blood eosinophilia

Markedly elevated IgE levels (>500 IU/mL)

Immediate skin test reactivity to Aspergillus antigen

Precipitating antibodies to Aspergillus species in the serum

Pulmonary infiltrates that may be migrating

Central bronchiectasis

* Although diagnosis does not require all 7 charactersitics, the

first 5 usually are present.

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Dr Khurana is a fellow in the division of pulmonary medicine and

critical care and Dr Tha her is a senior resident in the department

of

medicine, Jef ferson University Hospital, Philadelphia. Dr

Kane

is clinical associate professor of medicine, division of critical

care

and pulmonary, allergic and immunologic diseases, and program

director, internal medicine residency, Jefferson Medical College,

Jefferson University, Philadelphia.