Diagnosis: nitrofurantoin-induced lung disease
Nitrofurantoin (Macrodantin, Macrobid) is frequently used as first-line treatment for uncomplicated urinary tract infections (UTIs) and as prophylaxis for recurrent UTIs. Although generally well tolerated, it has a rare but serious side effect profile, including aplastic anemia, peripheral neuropathy, liver toxicity, and—as in the case of this patient—pulmonary toxicity.1
Nitrofurantoin-induced lung disease has an incidence of 3 cases per 1000 patients.2 Not surprisingly, elderly women are often affected, as this population is particularly susceptible to UTIs (and their recurrence), and thus are prescribed nitrofurantoin.3 The pathophysiology of the acute and chronic form of this drug reaction is unknown, but may be either an immunologic hypersensitivity reaction or a direct cytotoxic effect by nitrofurantoin or its metabolites on the lung parenchyma.4
The acute presentation begins within 3 weeks of initiation of nitrofurantoin. The most common symptoms include fever, dry cough, and dyspnea. Less common symptoms include an erythematous maculopapular rash, fatigue, arthralgias/myalgias, and anorexia. Patients may experience bronchospasm and have audible wheezing on exam. Eight percent of patients will have an abnormal chest radiograph, most often showing diffuse interstitial infiltrates or pleural effusions. An elevated WBC count appears in 40% of patients, many having an eosinophilia, and an elevated erythrocyte sedimentation rate may be present.5 Pulmonary function tests (PFTs), if performed, will show a restrictive pattern and a V/Q scan will show a ventilation-perfusion mismatch.2
The chronic presentation is much less common than the acute form. It occurs in patients on daily nitrofurantoin and its onset is delayed months to years after initiation of therapy. Symptoms are insidious and include cough and gradually worsening dyspnea on exertion. Physical exam may reveal wheezing or crackles and chest radiograph can show interstitial or alveolar infiltrates, as well as pleural effusions. Laboratory evaluation is similar to the acute form, and PFT findings also reveal a restrictive pattern.
Computed tomography has variable findings, such as ground-glass opacities, interstitial fibrosis, consolidation, peribronchial thickening, and centrilobular nodules. Lung biopsies have shown varying pathologic features: nonspecific interstitial pneumonia, pulmonary fibrosis, bronchiolitis obliterans organizing pneumonia, and hypersensitivity pneumonitis. 6,7