Nitrofurantoin-induced pulmonary fibrosis: a case report

Abstract

Introduction: Nitrofurantoin is a commonly used drug in the treatment and prevention of urinary tract infections. Many adverse effects of nitrofurantoin have been documented, including aplastic anemia, polyneuritis, and liver and pulmonary toxicity.

Case presentation: We describe the clinical history and the autopsy findings in a 51-year-old woman with lung fibrosis of unknown etiology. She had a history of recurrent urinary tract infections, treated with nitrofurantoin for many years. She was referred to our hospital for screening for lung transplantation because of severe pulmonary restriction and dyspnea. Unfortunately, she died as a result of progressive respiratory insufficiency. At autopsy bilateral patchy, sharply circumscribed fibrotic areas in the upper and lower lobes of the lungs were seen with honeycombing. Microscopically, end-stage interstitial fibrosis with diffuse alveolar damage was observed. Due to the atypical distribution of the fibrosis involving both the lower and upper lobes of the lung, the microscopic pattern of the fibrosis and the history of long-term nitrofurantoin use, we concluded that this drug induced the lung fibrosis. The recurrent urinary tract infections were probably caused by a diverticulum of the urinary bladder, which was discovered at autopsy.

Conclusion: This case shows that the use of nitrofurantoin may cause severe pulmonary disease. Patients with long-term use of nitrofurantoin should be monitored regularly for adverse pulmonary effects.

Figure 1

High resolution computed tomography (HR-CT) of the lung showing characteristics of fibrosis. (a) HR-CT at the level of the main carina. (b) HR-CT at the basal parts of the lungs 1 cm above the diaphragm. Inter- and intralobular septal thickening (IST), traction bronchiectasis (TB), honeycombing cysts (HC) and ground glass (GG) are indicated.

Figure 2

Transected lung showing randomly distributed areas of fibrosis with honeycombing and discrete islands of normal spongy lung tissue. Arrow: aspergilloma.

Figure 3

Hematoxylin and eosin, periodic acid Schiff, Grocott and Elastica von Gieson stained sections of sampled lung tissue. (a, b) Diffuse alveolar damage with denuded edematous alveolar septa with thick hyaline membranes and intra-alveolar hemorrhage. (c) Aspergilloma composed of radiating regularly branched fungal hyphae (periodic acid Schiff stain, insert: high magnification Grocott stain). (d, e, f) Lung parenchyma with severely distorted architecture consisting of established fibrosis with sharply angulated and cystically dilated bronchioli with inspissated secretions. In the interstitium a patchy lympho-histiocytic infiltrate is present (f). Bronchiolar smooth muscle hypertrophy (e) and squamous metaplasia (f) is seen.