Fungal disease Flashcards
What are the diagnostic criteria for chronic pulmonary aspergillosis?
- 1+ cavities with or without fungal ball OR nodules
- direct evidence of Aspergillus (microscopy, culture or IgG to Aspergillus)
- for at 3 months
- exclusion of alternative diagnoses
What is a simple aspergilloma?
- Subtype of chronic pulmonary aspergillosis
- Minimal/no symptoms
- Single cavity with fungal ball
- Direct evidence of aspergillus (as for CPA - microscopy, culture or IgG to Aspergillus)
- Immunocompetent
- No radiological progression over 3 months
What is cavitatory pulmonary aspergillosis (CCPA)?
- Subtype of chronic pulmonary aspergillosis
- Significant symptoms (resp and/or constitutional)
- 1+ cavities (+/- intraluminal material)
- Direct evidence of aspergillus (as for CPA - microscopy, culture or IgG to Aspergillus)
- Radiological progression over 3 months
What is chronic fibrosing pulmonary aspergillosis (CFPA)?
- Subtype of chronic pulmonary aspergillosis
- Complication of cavitatory pulmonary aspergillosis
- Severe destruction of 2+ lobes
- Major loss of lung function
- Fibrosis can manifest as consolidation or large cavities with surrounding fibrosis
What is the treatment for simple aspergilloma that is stable?
Nothing
What is the treatment for a simple aspergilloma with haemoptysis?
Resection if possible
Does antifungal therapy reduce morbidity and mortality in chronic pulmonary aspergillosis?
Yes if treatment longer than a year
What is first line treatment for chronic pulmonary aspergillosis?
Itraconazole
second line - voriconazole
third line - posoconazole or isavuconazole
fourth line - amphotericin B/micafungin/caspafungin
What are the side effects of itraconazole?
GI disturbance, heart failure, neuropathy, adrenal insufficiency
What are the side effects of voriconazole?
Photosensitivity, neuropathy, hair loss, hallucinations, rash, hepatitis, prolonged QT
What are the side effects of posaconazole?
GI disturbance, rash, hair loss, neuropathy
What are the side effects of isavuconazole?
GI disturbance, altered taste, hair loss, neuropathy, dizziness
What treatment monitoring do you need to do with azoles?
liver/renal, ECG, BP
What is the prevalence of azole resistance in chronic pulmonary aspergillosis?
5-10%
What gene is associated with azole resistance in aspergillosis?
cyp51A gene (most common in the promotor region)
What kind of hypersensitivity is ABPA?
Commonly type 1 but type 3&4 have been observed
What are the ISHAM criteria for ABPA?
- Predisposing condition (asthma, CF, bronchiectasis, COPD)
- Total IgE >1000 + Asp IgE >0.35/positive skin prick
- 2/3 of +ve Asp IgG (>27) /peripheral eosinophilia (>0.5) /pulmonary opacitites/central bronchiectasis
CT features of ABPA (note nothing specific)
- Cystic/varicose/saccular bronchiectasis. Central predominant
- thickened bronchial walls
- mucus plugging, bronchocele formation
- air trapping
- tree in bud
- areas of collapse
Can ABPA patients have elevated FeNO?
Yes because is T2 asthma phenotype (T2 = eosinophilic asthma)
What is the treatment for ABPA?
- Optimise asthma/bronchiectasis management
- oral glucocorticoids - 0.5mg/kg 2 weeks then 0.25mg/kg 4 weeks then taper by 5mg every 2 weeks
- consider pulse methylpred
What is second line treatment for ABPA?
- Azoles (itraconazole) - although not licensed
- Nebulised amphotericin B (Fungizone) - can cause bronchospasm
What is the effect of itraconazole on inhaled steroids?
Reduces metabolism therefore need to decrease dose (CYP3A4 inhibition)
What is aspergillus bronchitis and how is it diagnosed?
Diagnosis of exclusion. Need chronic productive cough (>4 weeks), repeated isolation of Aspergillus (or PCR) from sputum/BAL, Asp IgG >40mg/L. Gold standard is bronch showing mucoid impaction and biopsy showing hyphal infiltration
How is Aspergillus Bronchitis treated?
6week - 3month itraconazole
What is a diagnostic level of Aspergillus IgG?
Depends on disease. Need other tests alongside. >40mg/L abnormal, but need >90mg/L in CF. >90 common in ABPA but not diagnostic alone.
What is sub-acute invasive aspergillosis?
- Onset 1-3 months
- Moderate immunocompromise + pre-existing lung abnormalities
How is invasive aspergillosis treated?
Voriconazole
What is EORTC/MSG criteria fro proven invasive aspergillosis?
Biopsy demonstrating hyphal invasion with associated tissue damage OR Aspergillus cultured from a sterile site
What are EORTC/MSG crietria for probable invasive aspergillosis?
Mycology evidence of aspergillus (Asp IgG/ GM >0.5 serum or 0.8 BAL/positive sputum or BAL) + fitting radiological abnormality not otherwise explained (dense well-circumscribed lesion, air-crescent sign, cavity, wedge/segmental consolidation, tracheobronchial ulceration/pseudomembrane/plaque) + host factor (prednisolone >20mg/day, neutrophil low/abnormal, other specific immunosuppressants, decompensated cirrhosis, solid organ transplant, haematological malignancy/HSCT, HIV, severe viral pneumonia)
Are biologics used for ABPA?
May consider Omalizumab (anti-IgE) or Mepolizumab (anti-IL5)
How can you monitor for response to treatment of ABPA with steorids?
Measure total IgE - should decreased by 35%. Any rise>100% over baseline is an exacerbation.
Specific IgE/G to Asp don’t correlate to treatment response
