Suspected acute exacerbation of idiopathic pulmonary fibrosis associated with interferon alpha therapy for hepatitis C: case report
© Ling et al.; licensee Springer. 2013
Received: 29 October 2012
Accepted: 22 February 2013
Published: 12 March 2013
Interferon alpha (IFNα) has immune stimulatory actions implicated in its pulmonary toxicities. We describe deterioration of idiopathic pulmonary fibrosis (IPF) associated with IFNα treatment for chronic hepatitis C in a 58 year old woman culminating in a fatal suspected acute exacerbation of IPF (AE-IPF). Caution should be exercised in the use of IFNα in subjects with concomitant IPF given its known immunostimulatory effects and possible role in this suspected AE-IPF.
KeywordsIdiopathic pulmonary fibrosis / usual interstitial pneumonia Acute exacerbation of idiopathic pulmonary fibrosis Interferon alpha Hepatitis C
Pulmonary toxicity is a recognised complication of interferon alpha (IFNα), thought to be related to its immunostimulatory effects. IFNα has been shown to influence the immune system along multiple pathways including augmentation of proinflammatory and profibrotic cytokines (Midturi et al. 2004). Interstitial pneumonitis is the most commonly documented pulmonary toxicity of IFNα (Midturi et al. 2004), but potential deterioration of existing interstitial lung disease needs to be highlighted. We describe a case of progression of usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) during IFNα treatment, which culminated in a fatal acute exacerbation of IPF (AE-IPF).
Respiratory function tests of the patient with times in reference to her admission
9 months earlier
4 months earlier
FEV1 - L (% predicted)
FVC - L (% predicted)
FEV1/FVC (% predicted)
TLC – L (% predicted)
DLCO/VA - mL/min/mmHg/L (% predicted)
Discussion and evaluation
The immunostimulatory properties of IFNα and its recognised risks of pulmonary toxicity including pneumonitis create a strong case for implicating IFNα in potentiating the current deterioration of IPF with a possible contribution to the subsequent suspected AE-IPF. This patient demonstrated objective progression of her probable UIP soon after commencing IFNα, with both physiologic (within 1 month) and radiologic (within 2 months) evidence of deterioration. The 6% decline in FVC was felt to be within the limits of variability, although recent data have shown that FVC decline of >5% predicts a doubling of one year mortality (Zappala et al. 2010).
The acute respiratory decline during the described admission was suspected to be secondary to AE-IPF. Although P. aeruginosa and nmMRSA were isolated from respiratory specimens at the time, the patient received appropriate antibiotic therapy promptly at onset (prior to culture of the organisms) and subsequent bronchoscopy (performed because of progressive hypoxia) did not reculture Pseudomonas. Furthermore, her clinical course was marked by relentlessly progressive, antibiotic-unresponsive, hypoxic respiratory failure without evidence of sepsis, features much more consistent with AE-IPF than nmMRSA pneumonia. While exclusion of infection forms part of Collard’s proposed criteria for definition of AE-IPF (Collard et al. 2007), infectious agents have been found in up to one-third of subjects with this diagnosis (Borchers et al. 2011) and others have argued that diffuse alveolar damage superimposed upon IPF represents a common endpoint that may be the result of a range of potential triggers, including infection (Corte and Wells 2010).
Given that IFNα is now part of standard therapy for chronic HCV infection and the rising incidence of UIP/IPF in Western countries (Navaratnam et al. 2011), it is likely that subjects with UIP/IPF will be increasingly exposed to this therapy. The possibility that IFNα may result in significant, potentially fatal deterioration in underlying UIP/IPF necessitates careful consideration prior to embarking upon this therapy in these subjects. Whilst the current case in no way demonstrates causality, we would advise close monitoring and a low threshold for cessation of this therapy in the event of deterioration.
Acute exacerbation of idiopathic pulmonary fibrosis
Chronic obstructive pulmonary disease
Carbon monoxide diffusing capacity
Forced expiratory volume in one (1) second
Forced vital capacity
Hepatitis C virus
High resolution computed tomography
Idiopathic pulmonary fibrosis
Non-multiresistant methicillin resistant staphylococcus aureus
Total lung capacity
Usual interstitial pneumonia
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