Transcript 140714 KS Aspergillo..

Aspergillosis
Dr Katherine Syred
14/07/14
Aspergillosis
• Second most common human pathogen,
generally infects the lungs via the airways
• Causes four major types of human
disease.
• The different disease types affect different
types of patient
Condition
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(allergic bronchopulmonary
aspergillosis, ABPA)
hypersensitivity
pneumonitis
(chronic)
Aspergilloma
Chronic granulomatous
pueumonia
Invasive Aspergillosis
Definition
Patient Type
What is Aspergillus?
• Fungi can exist in hyphae or spore form
• Second most common fungal pathogen
humans
• Aspergillus is a mould and usually exists
as hyphae in the body
• It is a commensal in the environment and
does not usually affect the healthy
immunocompetent patient
Fungal Hyphae, 45-35˚acute angle
branching, 7-10 microns diam.
• In the lung parenchyma, little air is
available to the fungi which grows
anerobically by hyphae branching
• Aspergillus has several sub-species
including:
• Aspergillus fumagatus, flavus, niger
• Morphology- acute angle branching fungal
hyphae, 35-45 degrees, 3-6um
Hypersensitivity Pneumonitis
• “An immune mediated response to an
extrinsic antigen which involves both
immune complex and delayed
hypersensitivity reaction” (Robbins and
cottran)
Allergic Bronchopulmonary
Aspergillosis (ABPA)
• Specific large airways centred clinical
syndraome, asthmatics 1-2% and CF (79%
• Usually A. Fumigatus
Immune mediated
• History very important
How to diagnose allergic
bronchopulmonary aspergillosis
• Mechanism, production of cytokine IL 8
increased, can see eosinophils, T CD4/
CD8
• Bronchoalveolar lavage (BAL)– Cell count
shows increase lymphocytes• Th2 reaction (subset of CD4+) cells
implicated
• Proteolytic enzyme interrupts macrophage/
neutrophil killing hyphae/ spores
ABPA
•Airway plugging and dilatation with eosinophils
Distal bronchiole with plugging
Classical criteria diagnosis
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Clinical deterioration
Immediate positive skin test
Ig E >1000kU/L
A. fumagatus + ppt
Altered CXR
What does this look like in the
lung?
• ABPA: Bronchi can show asthmatic
changes (airway plugging/ smooth muscle
hyperplasia) but often changes more
pronounced in alveoli
• Small numbers of hyphae in mucus
• Numerous eosinophils/ cellular bedris in
mucus
Gross specimen, airway
plugging ABPA
• Cylindrical bronchiectasis of central airways, become
occluded by mucoid impaction.
• Atelectasis of a lobe, often upper. Squamous metaplasia
of airways.
Hypersensitivity Pneumonitis/
Extrinsic Allergic Alveolitis
• General term for abnormal TH1 response
in the lung to different allergens in different
contexts (NOT just Aspergillus)
What is the clinical syndrome?
1.Occupational high exposures may lead
to alveolitis in otherwise normal
individuals
• The antigens are different in different
environments:
• Brewer’s lung (A Clavatus)
• Farmers Lung (actinomyces)
• Pigeon keepers lung (bird dander)
• Popcorn workers lung (corn dust)
The spectrum allergic disease
caused by Aspergillus
(fumagatus)
occupational
Hypersensitivity
pneumonitis
High exposure/ normal immunity
Brewers lung
Aspergillus
idiopathic
Low exposure/ asthmatics/C.F
Allergic bronchopulmonary aspergillosis
How is hypersensitivity pneumonitis
diagnosed - 1
• HISTORY IS VITAL – detailed work and
social history/ pets/ hobbies. May need
inspection of home environment
• HISTORY of the disease:
• Exposure – Acute 4-6 hours, later fever/
SOB/ cough/ raised WCC
• Alleviated by a spell in hospital
Diagnosis 2
• Bronchoalveolar lavage – Histology can do
differential white cell count, raised is
lymphocytes indicative and specific
• Radiological appearance
• Video-assisted thoracoscopic (VATS)
biopsy if diagnosis is difficult
CT scan bilateral ground glass
infiltrates (acute)
• If the exposure to antigen continues, leads
to progressive tissue damage, airway
plugging, bronchocentric inflammation.
• Later chronic changes characteristic
multinucleate giant cells
• Can lead to irreversible fibrosis (UIP like)
• Vital to remove stimulating antigen
Early Hypersensitivity pneumonitis
• Bronchocentric inflammation
Treatment
• This is an abnormal/ excessive immune
response to an allergen in the airways
• Immunosupression will damped the bodies
excessive T-Cell response to allergen
• Steroids then cyclophosphmide etc
• Will prevent progression
• Also need to investigate house / work
place for vital erradication of allergen
source
Histological appearance
Foreign body granulomata
If not treated adequately and
stimulant antigen remains, ABPA/
Acute hypersensitivity
pneumonitis can progress to
Chronic hypersensitivity
pneumonitis
Chronic hypersensitivty
pneumonitis -leads to fibrosis
If Chronic hypersensitivity pneumonitis not treated,
progresses to end stage fibrosis “honeycomb lung”
(asbestosis/ other fibrotic lung diseases can look identical)
Colonising Aspergilloma
• Fungal Ball
• Occurs in cavities previously formed by:
-Old Tuberculosis
-Abscess
-Bronchiectasis
• No real invasion of tissues
• Different patients – previous cavitating
disease
CT Scan
How do these patients present?
• Recurrent haemopytysis
• Hx can help
• Very high aspergillus precipitin titre is vital
Differential diagnosis of
solitary pulmonary mass:
( get previous history)
•Tuberculous mass
•Carcinoma
•Hamartoma (benign tumour)
Histology
• Pink necrotic centre – dead cells and
debris
• Rim of active hyphae
Rim of
hyphae
Necrotic
centre
Fruiting bodies
• The air in the cavity allows the fungi to
undergo aerobic reproduction
Fruiting Bodies Contain Spores
• This is the ‘Aspergillium’
Treatment
• Depends on severity of symptoms
• Can be monitored over a number of years
and observed if stable
• May need FNAC/ biopsy to exclude other
pathology
• Can progress if patient become
immunosupressed
Chronic Granulomatous
Pneumonia
• Chronic granulomatous infection of the lung by
aspergillus species
• A Bronchocentric granulomatous inflammation
• Not angioinvasive, although can progress to this
• Prominent formation of granulomata
•(collections of macrophages)
Chronic Granulomatous
Pneumonia
• By definition has not become invasive
• Can progress to become invasive
• Need for exposure history and early
recognition/ treatment
Invasive Aspergillosis
• Usually originates from pulmonary
infection either de novo or from chronic
granulomatous aspergillosis
• Lung is susceptible to these tiny spores in
the environment
Who is susceptible
• Haematology/ paediatric cancer units –
especially if building work
• The immunocompromised, especially
neutropenia
• Immunosupressed host – DM, Steroids,
HIV, chemotherapy
• Chronic illnesses – ie diabetes mellitus,
asthma, mild immunosupression
How does Aspergillus colonise the
body?
• Breathed in through the airways
• Grows in the moist airway into the interstitium of
the lung
• Angio-invasion is a key feature – vascular
access leads to widespread dissemination
Patient’s CT scan (on methotrexate
for psoriatic arthritis, CAPD for renal
failure, also an amputee)
• Can then spread to bowel wall, liver,
kidneys
• Devastating disease, difficult to treat with
anti-fungals
Dissemination, angioinvasion
How do we diagnose this?
• Clinical history very important, low
threshold for adding anti fungals
immunosupression
• High index of suspicion ie haematology/
oncology wards
• In lung –imaging HRCT
• Brochoalveolar lavage - BAL
• Sputum
• Biopsy – lung/ bowel etc
Laboratory tests
• MICROBIOLOGY – sputum culture and
probe tests
• Serological tests – not yet in commercial
use
• (Can be difficult to detect)
• Sputum cytology and bronchial biopsy
histology – can be helpful
• Communicate with your microbiologists!
Aspergillus fumigatus
Aspergillus Niger
• www.doctorfungus.org/.../A_niger_1.jpg
Aspergillus niger is isolated from floor, carpet and mattress dust, acrylic paint, leather,
HVAC filters and fans, and potted plant soil.
Histology
• Acute necrotising inflammation with
plugging of vessels by fibrin
• Heavy infiltration by fungus
Other Fungi which can cause
similar invasive mycotic disease
• Mucormycoses – skin commensal, esp
history of surgery/ burns
• Can be angioinvasive and disseminate
• Again attacks a weakened patient
Broader Hyphae
Case Presentation
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Why did our patient not do so well?
Neuropaenic sepsis is an emergency!!
No prophylaxis/ early awareness
But he was investigated and treated
appropriately
• Severe/ fulminant mixed infections
• Underlying co-morbidities
• Mortality 60% overall!
Quick Case Study History
• Lady with alcoholism involved in RTC
Spain
• leg wounds may have been the port of
entry
• Mildly impaired cell mediated immunity in
alcoholism may have contributed.
• PM done by Dr Jo stafford,
Histopathologist in Crew Hospital. Thanks!
Myocardial abscess
Close up of myocardial abscess
Thyroid abscess
Close up of Thyroid abscess
Condition
Definition
Patient Type
(allergic bronchopulmonary
aspergillosis)
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Chronic hypersensitivity
pneumonitis
An immune mediated response
to an extrinsic antigen which
involves both immune complex
and delayed hypersensitivity
reaction
Heavy occupational
exposure
Low exposure
Asthmatics/ CF
Aspergilloma
A colonising fungal ball
in pre-existing cavity
Previous cavitating
lung disease
Chronic granulomatous
pueumonia
Granulomatous infection
confined to the lung
Mildly impaired T
cell immunity
Invasive Aspergillosis
Pulmonary infection
becomes angio-invasive
leading to widespread
lung and other organ
involvement
Impaired cell
mediated immunityImmunosupression
HIV
Diabetes Mellitus
Conclusions
• ANY QUESTIONS?
• References
• Robbins and Cottran,Pathologic Basis of
Disease, 7th edition, Kumar Abbas and
Fausto, Pages 399-400, page 739
• What is the other pathology cased by
aspergillus which has worldwide
significance?
• Afalotoxin produced by Aspergillus
• Causes Hepatocellular carcinoma (HCC),
high incidence in Asia
• HCC is a very rare cancer in the UK
Referrence
• Knutsen and Slavin , ABPA in Asthma and
Cystic Fibrosis, Review, Clinical and
developmental Immunology 2011,
1155/2011/843763