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 CXR.
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.
b) Briefly outline the specific management issues relating to diagnosis and treatment of this patient, excluding acute resuscitation.
a) Differential Diagnosis:
1. Bacterial/atypical Pneumonia
2. Opportunistic Infections:
a. Viral: Influenza/CMV/other Herpes Viruses
b. Fungal: Aspergillus/Cryptococcus
c. Other Organisms: PCP/PJP
3. Related to Rheumatoid Arthritis:
a. Methotrexate-induced pneumonitis
b. Rheumatoid Lung Disease
4. Acute cardiac failure e.g. secondary to valvular heart disease, ischaemic cardiomyopathy
b) Management issues:
1. Diagnostic investigations:
a. HRCT/CTPA
b. Bronchoscopy +/- lung biopsy (level of respiratory support may determine whether these investigations are possible)
c. Echo
2. Cease methotrexate
3. Steroids
a. Consider increasing the dose of steroid to cover "stress response"
b. Consider treatment dose associated with PCP/PJP treatment
c. Consider high-dose pulse of steroids
4. Empirical anti-infective treatment (complex decision, treatment may be associated with toxicity)
a. Broad spectrum antibiotic e.g. 3rd generation cephalosporin/aminoglycoside
b. Atypical cover
c. Oseltamivir
d. High dose Co-trimoxazole: monitor for Myelotoxicity
e. Gangcyclovir: monitor for Retinitis, Myelotoxicity
5. Specific treatment for cardiac disease
Differential diagnosis for bilateral pulmonary infiltrates should at first glance fall into the "is it infection or is it heart failure" territory. That would be the sensible approach. However, instead here is a long list of differentials.
Vascular:
Infectious
Neoplastic
Idiopathic
|
Drug-induced
Autoimmune
Traumatic
|
The college then asked for "specific management issues relating to diagnosis and treatment", which according to their model answer called for a salad of recommendations ranging from stopping immunosuppresive therapies ("cease methotrexate") to starting more immunosuppressive therapies ("consider high dose pulse of steroids"). It is of course difficult to assess the situation or determine what specific management or investigations are called for, even with the relatively extensive history given here. Unusually, the examiners have furnished us with some very relevant details:
The problem of non-specific lung disease appearing randomly and lethally among patients with poor immune systems is sufficiently common in the ICU, to the effect that multiple articles pop up if one searches for "diffuse pulmonary infiltrates in the immunocompromised".
To exclude non-infectious causes:
To investigate infectious causes:
Reasonable steps to prevent deterioration:
Some empirical management to cover for the usual suspects:
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.
Blanco, Silvia, and Antoni Torres. "Differential Diagnosis of Pulmonary Infiltrates in ICU Patients." www.antimicrobe.org
Danés, Cristina, et al. "Pulmonary infiltrates in immunosuppressed patients: analysis of a diagnostic protocol." Journal of clinical microbiology 40.6 (2002): 2134-2140.
Staszewski, Harry. "Diffuse pulmonary infiltrates in immunocompromised patients: Reconciling theory and practice." Postgraduate medicine 94.1 (1993): 69-78.
Fijen, J. W., et al. "Diffuse pulmonary infiltrates in immunocompromised patients." The Netherlands journal of medicine 55.1 (1999): 23-28.
Yousem, Samuel A., Thomas V. Colby, and Charles B. Carrington. "Lung biopsy in rheumatoid arthritis." American Review of Respiratory Disease 131.5 (1985): 770-777.
Gerard, Ludovic, et al. "Open Lung Biopsy in Nonresolving Acute Respiratory Distress Syndrome Commonly Identifies Corticosteroid-Sensitive Pathologies, Associated With Better Outcome." Critical care medicine 46.6 (2018): 907-914.
Mandell L.A, et al; "Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults" Clinical Infectious Diseases, Volume 44, Issue Supplement_2, 1 March 2007, Pages S27–S72, https://doi.org/10.1086/511159
Rodríguez, Alejandro, et al. "Impact of early oseltamivir treatment on outcome in critically ill patients with 2009 pandemic influenza A." Journal of antimicrobial chemotherapy66.5 (2011): 1140-1149.