228 - Fungal Disease Flashcards
what is allergic bronchopulmonary aspergillosis?
a hypersensitivity pneumonitis caused by aspergillus antigen in bronchi/aveoli
Hypersensitivity pneumonitis causes a immune mediated response, name the 2 pathways?
- Ty3 hypersensitivity reaction with cross linking of Th2 and B-cell mediated antibodies and antigens to form large immune complexes. These deposit in tissues causing an inflammatory response and vascular permeabilty
- Ty4 hypersensitvity reaction - delayed hypersensitivity reaction/cell mediated immune memory response with Th1 memory cells (previous aspergillus exposure) and macrophages - granulomas and inflammatory damage due to complement activation
what are the symptoms/signs of hypersensitivity pneumonitis?
- bronchospasm, mucous plugging, bronchocentric inflammation (bronchiectasis, smooth muscle hypertrophy and pulm. fibrosis)
- fever, dyspnoea, cough, wheeze, fine expiratory crackles
who is at risk from hypersensitivity pneumonitis?
px with underlying lung disease (asthma, COPD) as cant clear spores, pigeon fanciers, farmers, brewers, cheese workers, textiles
what investigations should be carried out in suspected hypersensitivity pneumonitis?
- peak flow/ spirometry for restrictive defects
- CXR - pulm infiltrates/consolidation (ring and glove signs )
- allergy testing - prick test
- sputum - evidence of hyphae
- bronchoalveolar lavage (↑WCC, ↑eosinophils, aspergillus present
- bloods for ↑IgE and aspergillus antibodies
- CT thorax - bilateral areas of consolidation and air trapping (ground glass infiltrates)
- VATS biopsy
what treatment should be given for hypersensitivity pneumonitis?
- oral corticosteroids (prednisolone) +/- oral antifungals
* immunosuppressants if necessary (cytophosphamide)
What is aspergilloma?
a pre-existing cavity in the lung parynchyma from previous cavitating disease (TB, abcess, bronciectasis, sarcoidosis) that has been colonised by aspergillus to form a mycetoma (fungal ball - pink necrotic centre of dead cells and debris surrounded by rim of active hyphae). Toxin released and cause erosion with haemoptysis
how does aspergilloma present?
- often asymptomatic
- haemoptysis in 50%
- solitary mass on CXR
- fever, cough, weight loss
how would you investigate suspected aspergilloma?
- CXR - solitary pulm mass with crescent if air around mass that can move if px moves
- biopsy/fine needle aspiration to exclude TB or neoplasia
- bloods - aspergillus antibodies raised
- sputum culture
- skin sensitivity
how should aspergilloma be treated?
- conservatively / monitoring
- oral antifungals eg itraconazole not very efficient
- surgical resection or bronchial artery embolisation for severe haemoptysis
What is Chronic Necrotising Pulmonary Aspergillosis?
Aspergillus colonises bronchi/alveoli any invades locally in those with mild/mod immunosuppression (alcoholism, steroid treatment, pre-existing lung disease). Bronchocentric granulomas formed by Th1.macrophage immune response - necrosis and cavitation
how does Chronic Necrotising Pulmonary Aspergillosis present?
- hx of exposure
* fever, productive cough +/- haemopytisis, night sweats, weight loss, consolidation
how should suspected Chronic Necrotising Pulmonary Aspergillosis be invesitgated?
- CXR - pum infiltrates/consolidation
- sputum culture
- broncho alveolar lavage / needle biopsy
- Galactomnnan Assay
- bloods - antibodies
how should Chronic Necrotising Pulmonary Aspergillosis be treated?
*antifungals - voriconazole, itraconazole, amphotericin
what is invasive apergillosis?
aspergillus colonisation of bronchi/alveoli and invasion of lung intersitium in immunosuppressed (neutropaenic - HIV, organ transplant, steroids, chemo). Angioinvasion occurs causing multiple lung infarcts
how does invasive apergillosis present?
- Hx of immunosuppression (neutropaenia) & exposure
- gravely ill, fever, cough, dyspnoea, pleuritic pain
- organ involvement
how would you investigate suspected invasive apergillosis?
- CXR - pulm infiltrates - multi-focal opacities “halo sign” due to film of blood
- sputum, bronchoalveolar lavage, biopsy
- galactomannan assay
how would you treat invasive apergillosis?
IV voriconazole or amphotericin plus flucytosine
*reduce immunosuppresants
what does the plasma membrane of a fungus consist of?
- phospholipid bilayer
- sterols - ergosterol
- embedded proteins
- synthases
what does the external cell walls of fungi consist of?
carbohydrate polymers - B glucans, chitinss, mannose sugars
*mannoproteins
how are fungal infections classified?
by region affected
- superficial and cutaneous (dermatophytosis, pityriasis versicolour, candidiasis)
- subcutaneous - rare and mainly travel associated
- systemic infections (invasive candidiasis, asperigillosis, cryptococcosis, pneumocytosis) also true pathogens (histoplasmosis, coccidiomycosis, blastomycosis, paracoccidiomycosis)
what is affected by dermatophytosis (tinea)?
localised infection of keratinised tissue (skin, hair, nails) spread by direct contact or indirect contact
what is pityriasis versicolor?
superficial infection of strateum corneum producing hyperpigmented or depigmented macules on trunk/proximal limbs caused by malassezia furfur - use ketoconazole shampoo topically or itraconazole/fluconazole orally
whar is superficial candidiasis?
superficial infection of mucous membranes (mouth vagian) with white patches and tinea like lesions caused by candida albicans
*invasive candidiasis in immunocompromised
what is cryptococcosis?
CNS infection or pulm infection in immunosuppressed caused by crptococcus neoformans via inhalation of fungal aerosols from soil
what is pneumocystosis?
infection of lungs by pneumocystis jiroveci (protozoan like fungus) in immunosuppressed - use co-trimoxazole
where do travel associated true pathogens come from?
- hystoplasmosis -east USA, Latin America, west africa
- coccidiomycosis - latin america
- blastomyscosis - E USA and canada
what investigations can be carried out to determine what fungus species?
- macroscopic exam - IV light for lesions, pus, bloody, necrosis - wood lamp to make fungi fluoresce
- microscopic exam
- culture - sugar agar plates - 1-3 weeks
- serology - rapid identification in systemic infection
what antifungals inhibit membrane synthesis?
azoles, echinocandins, allylamines
what antifungals inhibit membrane function?
polyenes
what antifungals inhibit nucleic acid synthesis and mitosis?
flucytosine (narrow spectrum so used with amphotericin IV- systemic candidiasis and cryptococcus) and griseofulvin
how do azoles work?
inhibit fungal cytochrome P450 enzyme which produces ergosterol necessary form cell membrane formation (also inhibits human p450 enzyme - toxicity) - inhibits growth, makes membrane permeable and builds up toxic sterol intermediates
name some imidazoles and what are they used for?
- ketoconazole, mionazole, clotrimazole
* candida and tinea
name some triazoles and what are they used for?
- fluconazole - candida, cryptococcus, dermatophytes - topical and oral but GI disturbances and liver damage
- voriconazole - life threatening candida, aspergillus -oral and IV (danger in renal impirment) - GI and visual impairment
- itraconazole - candida, aspergillus, cryptococcus - oral but mostly IV - negative ionotrope (less muscle contractions in heart) and liver damage
how do echinocandins like caspofungin work?
inhibit 1.3 beta glucan synthase and weakens cell wall. IV only and start with loading dose (caution in hepatic impairment) - few side effects
how do polyenes work?
increase membrane permeability by binding to ergosterol and increasing pore formation and ion leakage
- amphotericin - systemic aspergillis, candida, cryptococcus - IV or intrathecally (high protein bound) - high toxicity esp renal (hypokalaemia)
- nystatin - only topical against superficial candidiasis
how do allylamines work?
inhibit ergosterol synthesis by inhibiting squalene epoxidase enzyme
*Terbafine used for superficial dermatophyte infections top and oral - allergic skin reactions, GI disturbance and liver toxic
