Fungal disease Flashcards

1
Q

What are the diagnostic criteria for chronic pulmonary aspergillosis?

A
  • 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
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2
Q

What is a simple aspergilloma?

A
  • 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
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3
Q

What is cavitatory pulmonary aspergillosis (CCPA)?

A
  • 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
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4
Q

What is chronic fibrosing pulmonary aspergillosis (CFPA)?

A
  • 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
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5
Q

What is the treatment for simple aspergilloma that is stable?

A

Nothing

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6
Q

What is the treatment for a simple aspergilloma with haemoptysis?

A

Resection if possible

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7
Q

Does antifungal therapy reduce morbidity and mortality in chronic pulmonary aspergillosis?

A

Yes if treatment longer than a year

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8
Q

What is first line treatment for chronic pulmonary aspergillosis?

A

Itraconazole
second line - voriconazole
third line - posoconazole or isavuconazole
fourth line - amphotericin B/micafungin/caspafungin

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9
Q

What are the side effects of itraconazole?

A

GI disturbance, heart failure, neuropathy, adrenal insufficiency

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10
Q

What are the side effects of voriconazole?

A

Photosensitivity, neuropathy, hair loss, hallucinations, rash, hepatitis, prolonged QT

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11
Q

What are the side effects of posaconazole?

A

GI disturbance, rash, hair loss, neuropathy

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12
Q

What are the side effects of isavuconazole?

A

GI disturbance, altered taste, hair loss, neuropathy, dizziness

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13
Q

What treatment monitoring do you need to do with azoles?

A

liver/renal, ECG, BP

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14
Q

What is the prevalence of azole resistance in chronic pulmonary aspergillosis?

A

5-10%

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15
Q

What gene is associated with azole resistance in aspergillosis?

A

cyp51A gene (most common in the promotor region)

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16
Q

What kind of hypersensitivity is ABPA?

A

Commonly type 1 but type 3&4 have been observed

17
Q

What are the ISHAM criteria for ABPA?

A
  1. Predisposing condition (asthma, CF, bronchiectasis, COPD)
  2. Total IgE >1000 + Asp IgE >0.35/positive skin prick
  3. 2/3 of +ve Asp IgG (>27) /peripheral eosinophilia (>0.5) /pulmonary opacitites/central bronchiectasis
18
Q

CT features of ABPA (note nothing specific)

A
  • Cystic/varicose/saccular bronchiectasis. Central predominant
  • thickened bronchial walls
  • mucus plugging, bronchocele formation
  • air trapping
  • tree in bud
  • areas of collapse
19
Q

Can ABPA patients have elevated FeNO?

A

Yes because is T2 asthma phenotype (T2 = eosinophilic asthma)

20
Q

What is the treatment for ABPA?

A
  1. Optimise asthma/bronchiectasis management
  2. oral glucocorticoids - 0.5mg/kg 2 weeks then 0.25mg/kg 4 weeks then taper by 5mg every 2 weeks
  3. consider pulse methylpred
21
Q

What is second line treatment for ABPA?

A
  1. Azoles (itraconazole) - although not licensed
  2. Nebulised amphotericin B (Fungizone) - can cause bronchospasm
22
Q

What is the effect of itraconazole on inhaled steroids?

A

Reduces metabolism therefore need to decrease dose (CYP3A4 inhibition)

23
Q

What is aspergillus bronchitis and how is it diagnosed?

A

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

24
Q

How is Aspergillus Bronchitis treated?

A

6week - 3month itraconazole

25
Q

What is a diagnostic level of Aspergillus IgG?

A

Depends on disease. Need other tests alongside. >40mg/L abnormal, but need >90mg/L in CF. >90 common in ABPA but not diagnostic alone.

26
Q

What is sub-acute invasive aspergillosis?

A
  • Onset 1-3 months
  • Moderate immunocompromise + pre-existing lung abnormalities
27
Q

How is invasive aspergillosis treated?

A

Voriconazole

28
Q

What is EORTC/MSG criteria fro proven invasive aspergillosis?

A

Biopsy demonstrating hyphal invasion with associated tissue damage OR Aspergillus cultured from a sterile site

29
Q

What are EORTC/MSG crietria for probable invasive aspergillosis?

A

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)

30
Q

Are biologics used for ABPA?

A

May consider Omalizumab (anti-IgE) or Mepolizumab (anti-IL5)

31
Q

How can you monitor for response to treatment of ABPA with steorids?

A

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