1. Infeksi Jamur pada Paru
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2. Opportunistic Mycoses
• Most important fungal pathogens:
Candida
Aspergillus
Cryptococcus
Pneumocystis
Rhizopus
Mucor
Absidia
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3. Infections by Candida: Candidiasis
• Candida albicans
• Widespread yeast
• Infections can be short-lived, superficial skin
irritations to overwhelming, fatal systemic
diseases.
• Budding cells of varying size that may form both
elongate pseudohyphae and true hyphae
• Forms off-white, pasty colony with a yeasty odor
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4. Candida albicans
• Normal flora of oral cavity, genitalia, large intestine or
skin of 20% of humans
• Account for 80% of nosocomial fungal infections
• Account for 30% of deaths from nosocomial infections
• Thrush – occurs as a thick, white, adherent growth on
the mucous membranes of mouth and throat
• Vulvovaginal yeast infection – painful inflammatory
condition of the female genital region that causes
ulceration and whitish discharge
• Cutaneous candidiasis – occurs in chronically moist
areas of skin and in burn patients
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5. Clinical manifestations of
pulmonary candidiasis
• Cough productive of purulent
sputum, dyspnea, and fever
• The entirely nonspecific manifestations of
pulmonary involvement help to explain why it
is often not diagnosed until autopsy
• A typical case would be a patient with
faradvanced cancer developing a terminal
mixed pneumonia with bacteria and Candida

6. Chest roentgenograms of pulmonary
candidiasis
patchy or lobar infiltrates

7. Diagnosis and Treatment
• Presumptive diagnosis made if budding
yeast cells and pseudohyphae are found;
germ tube
• Growth on selective, differential media
differentiates Candida species
• Topical antifungals for superficial infections,
amphotericin B and fluconazole for
systemics
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8. Cryptococcosis and Cryptococcus neoformans
• Cryptococcus neoformans causes cryptococcosis.
• A widespread encapsulated yeast that inhabits soil
around pigeon roosts
• Common infection of AIDS, cancer or diabetes
patients
• Infection of lungs leads to cough, fever, and lung
nodules
• Dissemination to meninges and brain can cause
severe neurological disturbance and death.
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9. Diagnosis and Treatment
• Negative stain demonstrating encapsulated
budding yeast
• Biochemical tests, serological testing
• Systemic infection requires amphotericin B
and fluconazole.
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10. Pneumocystis (carinii) jiroveci and
Pneumocystis Pneumonia
• A small, unicellular fungus that causes
pneumonia (PCP), the most prominent
opportunistic infection in AIDS patients
• This pneumonia forms secretions in the
lungs that block breathing and can be
rapidly fatal if not controlled with
medication.
• Pentamidine and cotrimoxazole
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11. ASPERGILLOSIS
• Aspergilloma. (Fungus ball)
• ABPA. (Hypersensitivity)
• Aspergillus necrotizing bronchitis.
endo-bronchial mass, obstructive
pneumonitis, collapse, hilar mass.
• Invasive Pulmonary Aspergillosis.
Angioinvasive/ hemorrhagic infarcts.
Airway invasive-obstructing.

12. Saprophytic Aspergillosis
(Aspergilloma )
• Review of 60.000 CXR indentified 0.01 % prevelance.
• Infection without tissue invasion.
• Solid rounded mass, some times mobile.
• Fungal hyphae mixed with mucus and cellular debris
within a preexistent pulmonary cavity or ectatic
bronchus .
• If peripheral, Pleural thickening is characteristic.
• Mass is usually seperated from the cavity wall.

15. Saprophytic Aspergillosis
(Aspergilloma )
• Clinical findings could be non-specific.
• Some patients may remain asymptomatic.
• Most frequent symptom is HEMOPTYSIS 75%.
• Less commonly chest pain, dyspnea , malaise.
• Wheezing and fever (could also be secondary to
underlying disease, or bacterial super infection of the
cavity or aspergilloma itself).

16. Aspergilloma
• The most common predisposing factors are
tuberculosis and sarcoidosis.
• Other conditions that occasionally may be associated
with aspergilloma include bronchogenic cyst,
pulmonary sequestration, and pneumatoceles
secondary to Pneumocystis carinii pneumonia in
patients with (AIDS) .
• Bronchiectasis, ankylosing spondylitis, neoplasm.

17. Aspergilloma
• Tuberculosis is the most frequently associated
condition.
• Aspergilloma with history of tuberculosis. May
show multiple irregular fungus balls virtually
filling the pulmonary cavity

19. Aspergilloma
Radiography
• Presence of a solid, round or oval mass with soft-tissue
opacity within a lung cavity.
• Mass is separated from the wall of the cavity by an airspace of
variable size and shape "air crescent" sign seen in thin section
CT (mediastinal window).
• Other causes of the air crescent sign include angioinvasive
aspergillosis, echinococcal cyst, and, rarely, tuberculosis, lung
abscess, bronchogenic carcinoma, hematoma, and P carinii
pneumonia.

20. Aspergilloma
• Aspergillomas are often associated with thickening of the
cavity wall and adjacent pleura.
• Pleural thickening may be the earliest radiographic sign
before any visible changes are seen within the cavity.
• Associated scarring in lung lobes.
• Aspergillomas are usually single, they may also be
present bilaterally.
• Change in position.

23. CT

26. Aspergilloma
Mobile aspergilloma
• The aspergilloma usually moves when the patient
changes position .
• Chest CT scans obtained with the patient
supine and prone show a change in the
position of the aspergilloma within a
pulmonary cystic cavity.

28. • Mobile aspergilloma within a pulmonary cystic
cavity in a 43-year-old man. Chest CT scans
obtained with the patient supine (a) and
prone (b) show a change in the position of the
aspergilloma. A fumigatus was discovered at
bronchoscopy. (Courtesy of Josep M.
Mata, MD, Unidad Diagnóstica de Alta
Tecnología, Sabadell, Spain.)

33. Aspergilloma
Treatment
• In asymptomatic patients, No therapy needed.
• Medical therapy with bed rest, humidified
oxygen, cough suppressant, and postural drainage is
helpful in cases of mild hemoptisis.
• Surgical resection is indicated for patients with
severe life-threatening hemoptysis.
• Selective bronchial artery embolization can be
performed in those with poor lung function.

34. Aspergilloma
Antifungal therapy
• Patient is not a candidate for surgery
• Concomitant tissue invasion
• Itraconazole with some help
• Ampho B for invasive component.
• Newer Azoles, Voriconazole , Posaconazole
, and Ravuconazole.Their role is not clear.
• Antibiotics for bacterial superinfection.

35. Hypersensitivity Reaction (Allergic
Bronchopulmonary Aspergillosis)
• ABPA is seen most commonly in patients with long-
standing bronchial asthma (7-14%) or CF (6%) .
• Characterized by the presence of plugs of mucus
containing Aspergillus organisms and eosinophils.
• This results in bronchial dilatation typically involving
the segmental and sub segmental bronchi.

36. Allergic Bronchopulmonary
Aspergillosis
• ABPA is caused by a complex hypersensitivity
reaction to Aspergillus organisms.
• The fungi proliferate in the airway lumen , producing
a constant supply of antigen.
• A type I hypersensitivity reaction with IgE and IgG
release occurs.
• Immune complexes and inflammatory cells are then
deposited in the bronchial mucosa.
• Production of necrosis and eosinophilic infiltrates
(type III reaction) with bronchial wall damage and
bronchiectasis.

37. Allergic Bronchopulmonary
Aspergillosis
• Excessive mucus production and abnormal ciliary
function lead to mucoid impaction.
• Many patients cough up thick mucous plugs in which
hyphal fragments can be demonstrated at culture or
histologic analysis.
• Acute clinical symptoms include recurrent wheezing,
malaise with low-grade fever, cough, sputum
production, and pleuritic chest pain.
• Patients with chronic ABPA may also have a history of
recurrent pneumonia.

38. Allergic Bronchopulmonary Aspergillosis
Radiologic manifestations
• Homogeneous, tubular, finger-in-glove areas of
increased opacity in a bronchial distribution, usually
predominantly involving the upper lobes.
• Band like opacities related to plugging of airways by
hyphal masses with distal mucoid impaction and can
migrate from one region to another.
• Occasionally, isolated lobar or segmental atelectasis may
occur.

39. Allergic Bronchopulmonary Aspergillosis
• In later stages central bronchiectasis and pulmonary
fibrosis develop.
• CT findings in ABPA consist primarily of mucoid
impaction and bronchiectasis involving
predominantly the segmental and sub segmental
bronchi of the upper lobes .
• In approximately 30% of patients, the impacted
mucus has high attenuation or demonstrates frank
calcification at CT.

41. • .

43. Allergic Bronchopulmonary Aspergillosis
Diagnostic criteria
• Asthma.
• Immediate skin reactivity to Aspergillus.
• Serum precipitins to A fumigatus.
• Total serum IgE >1.000 ng/ml
• Current or previous pulmonary infiltrates.
• Central Bronchiectasis.
• Peripheral Eosinophilia.

44. Allergic Bronchopulmonary Aspergillosis
Stages /Patterson et all
• Stage 1 ( Acute stage)
• Stage 2 ( Remission stage)
• Stage 3 ( Exacerbation stage)
• Stage 4 ( Steroid dependent stage)
• Stage 5 ( Fibrotic stage)

45. Allergic Bronchopulmonary Aspergillosis
Treatment
• Oral corticostroids, relief of bronchospasm, clearing
of pulmonary infiltrates and decrease IgE levels( 0.5
mg/kg/d for 2 wks then taper).
• Most patients require prolonged low dose therapy.
• Itraconazole low dose(200 mg bid for 16 weeks) can
Help in 50% reduction of corticosteroid dose. With
no significant toxicity.

46. Allergic Bronchopulmonary Aspergillosis
Syndromes Related to ABPA
• Mucoid Impaction
Without asthma, mucus plug lead to atelectasis.
Usually presents with cough.
• Bronchocentric Granulomatosis.
Necrotizing granulomas, obstruct and destroy
bronchiols . Eosinophilic inflamatory infiltrate and
fibrosis with no tissue or vascular invasion by
aspergillus, almost always asthmatics with persistent
cough and high IgE levels. good response to
corticosteroids.

47. Allergic Bronchopulmonary Aspergillosis
• Eosinphilic pneumonitis
Rarely caused by aspergillus, cough dyspnea and fever
with peripheral pulmonary infiltrate, diagnosis made
by biopsy, good response to corticosteroids.
• Hypersesitivity pneumonitis
Extrinsic allergic alveolitis, intense repeated
inhalation of thermophilic bacteria, fungi, bird
excreta, and chemical agents causes hypersensitivity
granulomatous inflamation of distal airway disease.

48. Semi-invasive (Chronic Necrotizing)
Aspergillosis
Predisposing factors
• Chronic debilitating illness, Advanced age.
• Alcoholism, Malnutrition.
• DM, CF, COPD.
• Prolonged steroid therapy, Radiation therapy.
• Inactive TB.
• Pneumoconiosis.
• Sarcoidosis.

49. Semi-invasive (Chronic Necrotizing)
Aspergillosis
Symptoms
• Often insidious and include chronic cough, sputum
production, fever, and constitutional symptoms.
• Hemoptysis has been reported in 15% of affected
patients .
• May manifest with chronic bronchitis and
recurrent episodes of mild hemoptysis.

50. Semi-invasive (Chronic Necrotizing)
Aspergillosis
• In patients with COPD, may manifest with non-
specific clinical symptoms such as cough, sputum
production, and fever lasting more than 6 months.

51. Semi-invasive (Chronic Necrotizing)
Aspergillosis
Radiologic manifestations
• Thin-section CT scan (lung window) shows
unilateral or bilateral rounded segmental areas
of consolidation with or without cavitation or
adjacent pleural thickening,
• Multiple nodular areas of increased opacity .
• The findings progress slowly over months or years.

58. Semi-invasive (Chronic Necrotizing)
Aspergillosis
Diagnosis Criteria
• Clinical and Radiologic features
• Isolation of Aspergillus species by culture from
sputum, bronchoscopic or percutaneous
samples.
• Exclusion of other conditions

59. Semi-invasive (Chronic Necrotizing)
Aspergillosis
Treatment
• Antifungals should be initiated once the
diagnosis is made. IV Ampho B, Itraconazole is
also effective.
• Surgical resection for healthy individuals with
good lung reserves, not tolerating antifungals
or where antifungals are ineffective in setting
of active disease.

60. Invasive Pulmonary Aspergillosis (IPA)
Major risk factors.
• Prolonged neutropenia >3 wks or neutrophil
dysfunction.
• Corticosteroid therapy (prolonged, high dose).
• Transplantation (Lung and BM )
• Hematologic malignancy( leukemia)
• Cytotoxic therapy.
• AIDS.

62. Airway-invasive Aspergillosis
• The presence of Aspergillus organisms deep to the
airway basement membrane.
• It occurs most commonly in immunocompromised
neutropenic patients and in patients with AIDS.
• Clinical manifestations include acute
tracheobronchitis, bronchiolitis, and
bronchopneumonia.

63. Airway-invasive Aspergillosis
• Patients with acute tracheobronchitis usually have
normal radiologic findings.
• Occasionally, tracheal or bronchial wall thickening
may be seen.
• Bronchiolitis is characterized at HRCT by the
presence of centrilobular nodules and branching
linear or nodular areas of increased attenuation
having a "tree-in-bud“ appearance.

64. Airway-invasive Aspergillosis
• The centrilobular nodules have a patchy
distribution in the lung.
• Aspergillus bronchopneumonia results in
predominantly peribronchial areas of
consolidation.
• Rarely, the consolidation may have a lobar
distribution.

65. Airway-invasive Aspergillosis
Obstructing bronchopulmonary aspergillosis
• noninvasive form of aspergillosis.
• Characterized by the massive intraluminal
overgrowth of Aspergillus species.
• Usually A fumigatus, in patients with AIDS .
• Affected patients exhibit cough, fever, and new onset
of asthma.
• Patients may cough up fungal casts of the bronchi
and present with severe hypoxemia.

66. Airway-invasive Aspergillosis
CT findings in obstructing bronchopulmonary
aspergillosis
• Mimic those in allergic bronchopulmonary
aspergillosis.
• Bilateral bronchial and bronchiolar dilatation.
• large mucoid impactions (mainly lower lobes).
• Diffuse lower lobe consolidation caused by
postobstructive atelectasis.

68. Angioinvasive Aspergillosis
• Angioinvasive aspergillosis occurs almost
exclusively in immunocompromised patients
with severe neutropenia.
• For many reasons, however, there has been a
substantial increase in the number of patients
at risk for developing invasive aspergillosis.

69. Angioinvasive Aspergillosis
These reasons includes
• Development of new intensive chemotherapy
regimens for solid tumors.
• Difficult-to-treat lymphoma, myeloma, and resistant
leukemia.
• Increase in the number of solid organ
transplantations.
• Increased use of immunosuppressive regimens for
other autoimmune diseases.

70. Angioinvasive Aspergillosis
• Despite having a normal neutrophil count, affected
patients have functional neutropenia because the
function of the neutrophils is inhibited by the use
of high-dose steroids.
• Invasion and occlusion of small to medium-sized
pulmonary arteries by fungal hyphae.
• This leads to the formation of necrotic
hemorrhagic nodules or pleura-based, wedge-
shaped hemorrhagic infarcts.

71. Angioinvasive Aspergillosis
Characteristic CT findings
• Nodules surrounded by a halo of ground-glass
attenuation "halo sign“ or pleura-based, wedge-
shaped areas of consolidation.
• These findings correspond to hemorrhagic infarcts.
• In severely neutropenic patients, the halo sign is
highly suggestive of angioinvasive aspergillosis.

72. Angioinvasive Aspergillosis
• However, a similar appearance has been
described in a number of other conditions.
• Infection by Mucorales and Candida.
• Herpes simplex and cytomegalovirus.
• Wegener granulomatosis, Kaposi sarcoma ,
and hemorrhagic metastases .

73. Angioinvasive Aspergillosis
• Separation of fragments of necrotic lung from
adjacent paren-chyma results in air crescents
similar to those seen in mycetomas.
• The air crescent sign in angioinvasive
aspergillosis is usually seen during
convalescence (ie, 2–3 weeks after initiation
of treatment and concomitant with resolution
of the neutropenia).

81. Angioinvasive Aspergillosis
Diagnosis
• The clinical diagnosis is difficult, and the mortality
rate is high.
• Positive culture Methanamine silver, PAS
• BAL 97% specific. But less sensitive.
• Chest CT findings, Halo sign, Cresent sign.
• Open or thoracoscopic lung biopsy is the gold
standard.

82. Invasive Pulmonary Aspergillosis (IPA)
Treatment
• Start empiric therapy, when diagnosis
suspected.
• Most commonly used medicine Ampho B 0.6
– 1.2 mg/kg/d , in severly
immunocomromized 1 -1.5 mg/kg/d.
• Duration depends on the period of
immunosuppression. response 20-83%.

83. Invasive Pulmonary Aspergillosis (IPA)
• Other treatment options
• Itraconazol 200-400 mg/d , 39% response.
• Could be used in less immunocompromised.
• Late stage therapy after initial control of
Ampho B.
• Combination therapy , no great efficacy.
• Caspofungin ,recently approved medicine.
• Voriconazole, Posaconazole.

84. Invasive Pulmonary Aspergillosis (IPA)
• Voriconazole vs Ampho B, (391 pt randomized ).
Succesfull response rate
49.7% for Vorico arm, 27.8% for Ampho B.
Herbrecht et al, NEM 347: 408 (2002).
• Caspofungin, 70% favorable response in pulm.
disease for salvage therapy, daily dose.
• Ampho B + Caspo ,
• Vori + Caspo, combination better out come.
marr et al, clin inf . Dis 2003.

85. Invasive Pulmonary Aspergillosis (IPA)
Surgical resection
• Massive hemoptysis.
• Localized lesion.
• Continuing immunosuppression.
• Further immunosuppressive therapy.
• Outcome is poor in BMT, Pt on mechanical
ventilation and those who have multiple foci
of infection.

86. Invasive Pulmonary Aspergillosis (IPA)
• Outcome of therapy
• Early diagnosis.
• Recovery of underlying host defense defect.
• Resolution of neutropenia,
• Taper of immunosupressive therapy.
• Disease limited to the lung.

87. THANK YOU
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