Question 14

A 57-year-old female has required intubation and mechanical ventilation for hypoxaemic respiratory failure with symptoms of cough and dyspnoea that have been gradually progressive over 4 weeks. There is a diffuse bilateral infiltrate on her chest X-ray. She has a history of rheumatoid arthritis and is receiving treatment with methotrexate and prednisolone and has no previous history of respiratory disease.

a)    List the likely differential diagnosis.    (20% marks)

b)    Briefly outline the specific management issues relating to diagnosis and treatment of this patient, excluding acute resuscitation.    (80% marks)

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College answer

Not available.


This question is identical to Question 20 from the first paper of 2014.

List the likely differential diagnosis  here is only worth only 20% which means that a table of this size would be completely unreasonable.

Differential Diagnosis for Diffuse Bilateral Pulmonary Infiltrates


  • Pulmonary haemorrhage
  • Cardiogenic pulmonary oedema


  • Bacterial
  • Viral
  • Fungal
  • PJP


  • Lymphangitis
  • Infiltrative neoplasm


  • ARDS


  • Eosinophilic pneumonitis
  • Organising pneumonia
  • Alveolar haemorrhage
  • Methotrexate-induced


  • Goodpastures (haemorrhagic)
  • Rheumatoid pneumonitis
  • Graft vs host disease in BMT
  • Engraftment syndrome


  • Bilateral atelectasis
  • Pulmonary contusions

Specific management issues relating to diagnosis and treatment: 

To exclude non-infectious causes:

  • A transthoracic echo will inevitably be informative, but the finding of a poor systolic function is not going to exclude infectious aetiology (which could easily co-exist with heart failure, as a wet lung is the devil's playground)
  • HRCT is suggested by the college, and this may give some information regarding the pattern of the disease, while not being particularly diagnostic (the CTPA would reveal emboli, but surely a gradual onset over four weeks does not particularly resemble the natural history of a PE)
  • A "vasculitic screen", whatever that might be in the local parlance - mainly to exclude something like Wegener's or Goodpasture's syndromes (though these are made unlikely by the immunosuppression) 

To investigate infectious causes:

  • Perform a bronchoscopy and send lavage specimens for multiple tests:
    • Bacterial cultures and gram stain
    • Acid-fast bacilli
    • Cell count (also looking for weird stuff like eosinophilic pneumonitis)
    • P.carinii PCR
    • Aspergillus PCR
    • Respiratory viral nucleic antigen tests, including CMV, HSV and VZV
    • Cryptococcal antigen
    • COVID19 rapid antigen test
  • Urinary antigens for Streptococcus and Legionella
  • Atypical pneumonia serology, looking for antibodies to mycobacteria, ChlamydiaCoxiella, etc.

Reasonable steps to prevent deterioration:

  • Cease methotrexate. The disease process progressed while the patient (presumably) continued to dutifully take her methotrexate and steroids; ergo it is less likely to be an autoimmune disease driven by B-cells and auto-antibodies.
  • Be moderate with fluid resuscitation, as this has been demonstrated to have a negative impact in ARDS
  • Ventilate the patient with lung-protective low tidal volumes, high PEEP and minimal driving pressures

Some empirical management to cover for the usual suspects:

  • Cover P.jirovecii with therapeutic dose of sulfamethoxazole/trimethoprim; 
  • Cover gram-positive and gram-negative organisms with something broad, as the stakes are high and there will always be opportunity to narrow the antibiotics once cultures are available. Some combination of meropenem azithromycin and either vancomycin or linezolid are recommended by various guideline-writers (eg. the parts of the 2016 IDSA guidelines which mention "critically ill patients")
  • Antifungal therapy might become relevant if fungi are implicated by culture results
  • Antiviral therapy (oseltamivir) is suggested by the college in their answer to Question 20 from the first paper of 2014, in the ake of the H1N1 pandemic. In this day and age, one would probably score marks by mentioning remdesivir and baricitinib.

If things are not going as planned (i.e. it's a week down the track and the patient is not getting better), a lung biopsy might be indicated. Apparently, it often identifies steroid-responsive pathology (Gerard et al, 2018), in which case the college's suggestion (massive doses of methylprednisolone) becomes relevant. 


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