Azathioprine-associated interstitial pneumonitis

Area of Science:

• Pulmonology
• Nephrology
• Immunosuppression

Background:

• Renal allograft recipients often receive immunosuppressants like azathioprine (Imuran).
• Pulmonary complications can arise in transplant patients, necessitating differential diagnosis.

Purpose of the Study:

• To investigate the potential for azathioprine to cause pulmonary toxicity in renal transplant recipients.
• To characterize the histological findings and clinical outcomes associated with azathioprine-induced lung disease.

Main Methods:

• Retrospective analysis of seven renal allograft recipients presenting with pulmonary infiltrates.
• Review of clinical data, lung biopsy findings (histopathology, ultrastructural analysis), and response to azathioprine withdrawal.
• Cytological examination of brushing specimens for atypical epithelial cells.

Main Results:

• Seven patients developed bilateral pulmonary infiltrates and hypoxemia unresponsive to antibiotics.
• Lung biopsies showed diffuse alveolar damage (DAD) or usual interstitial pneumonia (UIP), progressing to fibrosis.
• Discontinuance of azathioprine led to clearing of infiltrates in DAD cases; UIP cases had high mortality.
• Dose-dependent histological changes were observed, with higher cumulative doses associated with atypical epithelial hyperplasia and fibrosis.
• Ultrastructural changes were similar to other drug-induced pulmonary toxicities.

Conclusions:

• Azathioprine is implicated as a cause of direct, dose-dependent pulmonary toxicity.
• Drug-associated diffuse interstitial pulmonary disease should be considered in renal transplant patients on azathioprine with lung infiltrates.
• Histological patterns (DAD vs. UIP) correlate with prognosis and response to drug withdrawal.